Article

Density and organization of free nerve endings in the corneal epithelium of the rabbit

November 1982
Pain 14(2):105-120

DOI:10.1016/0304-3959(82)90092-6

Authors:

Andrew Rozsa

Southern Pain Specialists

Roger W Beuerman

Singapore Eye Research Institute

Many questions regarding the organization and the density of corneal intraepithelial terminals remain unanswered in spite of the extensive work that has been done on corneal innervation.In the present study, we employed light microscopic observations of gold-impregnated, serial cross-sections of rabbit cornea to document the assumed, but hitherto uncalculated high density of intraepithelial terminals. Our results showed that the innervation density of corneal epithelium was about 300–600 times that of skin and 20–40 times that of tooth pulp. The density of epithelial innervation was seen to decrease from the center of the cornea to the periphery.Serial cross-sections and flat mounts were used in the three-dimensional reconstruction of the organizational design of corneal terminals. From the subepithelial plexus, axons were seen to penetrate the epithelium, forming terminals that either diverged or branched vertically and horizontally. The vertical axons extended toward the outer cell layer. Horizontal axons developed into families of leashes with disorganized terminal branches and endings.The density and organizational geometry of corneal terminals, together with the correlations between their anatomical uniqueness and the types of sensations elicited by their stimulation, suggest that the cornea is a useful model for the study of experimental acute pain.

The Role of Sensory Innervation in Homeostatic and Injury-Induced Corneal Epithelial Renewal

Article

Full-text available

Aug 2023
INT J MOL SCI

The cornea is the window through which we see the world. Corneal clarity is required for vision, and blindness occurs when the cornea becomes opaque. The cornea is covered by unique transparent epithelial cells that serve as an outermost cellular barrier bordering between the cornea and the external environment. Corneal sensory nerves protect the cornea from injury by triggering tearing and blink reflexes, and are also thought to regulate corneal epithelial renewal via unknown mechanism(s). When protective corneal sensory innervation is absent due to infection, trauma, intracranial tumors, surgery, or congenital causes, permanent blindness results from repetitive epithelial microtraumas and failure to heal. The condition is termed neurotrophic keratopathy (NK), with an incidence of 5:10,000 people worldwide. In this report, we review the currently available therapeutic solutions for NK and discuss the progress in our understanding of how the sensory nerves induce corneal epithelial renewal.

АСИММЕТРИЯ НЕЙРОСЕТЕЙ ПОКОЯ ПО ДАННЫМ ФМРТ

Article

Oct 2023

В статье представлен всесторонний обзор функциональной асимметрии во внутренних сетях связности, выявленной с помощью фМРТ в состоянии покоя. Сделана попытка суммировать ключевые выводы о латерализации множественных сетей и связанных с ними когнитивных последствиях. Во введении объясняется, как фМРТ в состоянии покоя позволила изучить функциональную асимметрию путем картирования коррелированных спонтанных колебаний нейронной активности. Феномен асимметрии охватывает различные сети в состоянии покоя и когнитивные области, что представляет собой сложную задачу для расшифровки основных механизмов функциональной асимметрии. В разделе основные данные о сетевой асимметрии рассматриваются доказательства доминирования левого и правого полушарий в основных функциональных сетях: Сети языка и семантической памяти демонстрируют, как правило, левостороннюю латерализацию у правшей, что соответствует языковой специализации левого полушария. Это хорошо выражено у правшей, и более вариабельно у левшей. Также отмечено незначительное влияние доминирования глаз на асимметрию зрительной сети. Зрительно-пространственная обработка демонстрирует правую латерализацию, вне зависимости от правшества и левшества. Сеть режима по умолчанию (DMN) проявляет сложную «смешанную» латерализацию в центральных областях, часто билатеральную, но с более четкой асимметрией в передних/задних областях. Правши склонны к левой латерализации, тогда как левши демонстрируют уменьшенную или обратную асимметрию. Обсуждаются клинические последствия, в том числе то, как психические расстройства нарушают типичные модели латерализации. Рассмотрены структурные и функциональные факторы, способствующие асимметрии сети. В обзоре подчеркивается значительная индивидуальная вариабельность латерализации, на которую влияют рука, пол, возраст и неизвестные генетические/эмпирические факторы. ФМРТ в состоянии покоя выявляет сложность функциональной асимметрии мозга, выходящую за рамки классических моделей. Наконец, предлагаются будущие направления исследований, в том числе использование расширенного сетевого анализа и мультимодальной визуализации для выяснения принципов специализации полушарий. В целом, в работе подчеркивается, как подходы к связям в состоянии покоя расширили наше понимание функциональной асимметрии мозга. This article provides a comprehensive overview of functional asymmetries in intrinsic connectivity networks revealed by resting-state fMRI. An attempt is made to summarize key findings about the lateralization of multiple networks and their associated cognitive consequences. The introduction explains how resting-state fMRI has enabled the study of functional asymmetries by mapping correlated spontaneous fluctuations in neural activity. The phenomenon of asymmetry spans various networks in resting states and cognitive domains, which poses a challenge to decipher the underlying mechanisms of functional asymmetry. The Basic Evidence for Network Asymmetry section examines evidence for left- and right-hemisphere dominance in core functional networks: Language and semantic memory networks tend to exhibit left-sided lateralization in right-handers, consistent with left-hemisphere language specialization. This is well expressed in right-handed people, and more variable in left-handed people. There was also a slight effect of eye dominance on visual network asymmetry. Visuospatial processing demonstrates right lateralization, regardless of right-handedness or left-handedness. The default mode network (DMN) exhibits complex “mixed” lateralization in central regions, often bilateral, but with more distinct asymmetries in anterior/posterior regions. Right-handers tend to exhibit left lateralization, whereas left-handers exhibit reduced or reverse asymmetry. Clinical implications are discussed, including how psychiatric disorders disrupt typical lateralization patterns. Structural and functional factors contributing to network asymmetry are considered. The review highlights the significant interindividual variability in lateralization, which is influenced by hand, sex, age, and unknown genetic/empirical factors. Resting-state fMRI reveals the complexity of functional brain asymmetries beyond classical models. Finally, future research directions are suggested, including the use of advanced network analysis and multimodal imaging to elucidate principles of hemispheric specialization. Overall, the work highlights how resting-state connectivity approaches have expanded our understanding of functional brain asymmetries.

ФУНКЦИОНАЛЬНАЯ МЕЖПОЛУШАРНАЯ АСИММЕТРИЯ МОЗГА И АДАПТАЦИЯ

Article

Oct 2023

А.И. Боравова

Функциональная асимметрия является фундаментальным принципом организации мозга человека, при котором каждое полушарие играет различную роль в процессах адаптации. Хотя асимметрия является типичной, в норме существуют значительные различия в степени и направлении латерализации у разных людей. Причины и последствия этой вариабельности остаются не до конца понятными. Популяционные исследования показывают, что крайне нетипичная асимметрия встречается редко и может свидетельствовать о нарушении развития. Однако более скромные различия в латерализации, вероятно, представляют собой адаптивную пластичность, поскольку нейронные цепи настраиваются на способности и опыт индивидуума. В обзоре анализируется вклад российских ученых в решение этой проблемы. Functional asymmetry is a fundamental principle of human brain organization in which each hemisphere plays a different role in adaptation processes. Although asymmetry is typical, there is considerable normal variability in the degree and direction of lateralization across individuals. The causes and consequences of this variability remain not fully understood. Population studies suggest that highly atypical asymmetry is rare and may indicate a developmental disorder. However, more modest differences in lateralization likely represent adaptive plasticity, as neural circuits adjust to an individual's abilities and experiences. This review analyzes the contribution of Russian scientists to this problem.

ЦИРКАДНЫЙ РИТМ ГИДРОДИНАМИКИ ГЛИМФАТИЧЕСКОЙ СИСТЕМЫ

Article

Full-text available

Oct 2023

Alexander Kholmanskiy

О связи гидродинамики глимфатической системы мозга с суточным ритмом свидетельствуют суточные корреляции температурных зависимостей (TDs) физико-химических свойств физиологических жидкостей и воды. Динамика водородных связей в объемной и гидратированной воде определяла энергии активации TDs ионных токов потенциал зависимых каналов, регулирующих сигнальные и трофические связи в нейропиле корковой паренхимы. Физика минимизации TD изобарной теплоемкости воды позволила объяснить стабилизацию и функциональную оптимизацию термодинамики жидкостей глазного яблока при 34.5 °C и мозга человека во сне при 36.5 °C. При этих температурах терморецепторы роговицы и клетки ганглиозного слоя сетчатки через связи с супрахиазматическим ядром и эпифизом переключают циркадный ритм гидродинамики крови и спинномозговой жидкости с дневного на ночной режим. Филогенез циркадного ритма отобразился в зависимости длительности ночного сна млекопитающих от диаметра глазного яблока и массы эпифиза. Активность всех нервов глазного яблока обусловила разбиение ночного метаболизма мозга на NREM and REM фазы. Этим фазам соответствуют два режима глимфатической системы – электрохимический и динамический. Первый отвечает за релаксационные процессы синаптической пластичности и химическую нейтрализацию токсинов с участием воды и мелатонина. Быстрое движение глаз и увеличение мозгового кровотока во втором режиме усиливают водообмен в паренхиме и вымывание токсинов в венозную систему. Электрофизику клиренса и проводимость ионных и водных каналов мембран кровеносных сосудов и астроцитов модулируют осцилляции поляризационных потенциалов дипольных доменов воды в пристеночных слоях плазмы артериол и капилляров. he connection between the hydrodynamics of the brain glymphatic system and the circadian rhythm is evidenced by diurnal correlations of temperature dependencies (TDs) of physicochemical properties of physiological fluids and water. The dynamics of hydrogen bonding in bulk and hydrated water determined the activation energies of TDs of ionic currents of potential dependent channels regulating signaling and trophic connections in the neuropil of cortical parenchyma. The physics of TD minimization of the isobaric heat capacity of water helped to explain the stabilization and functional optimization of the thermodynamics of eyeball fluids at 34.5 °C and of the human brain in sleep at 36.5 °C. At these temperatures, corneal thermoreceptors and retinal ganglion cells through connections with the suprachiasmatic nucleus and epiphysis switch the circadian rhythm of blood and cerebrospinal fluid hydrodynamics from daytime to nighttime mode. The phylogeny of the circadian rhythm was displayed in the dependence of the duration of nocturnal sleep-in mammals on the diameter of the eyeball and the mass of the epiphysis. The activity of all nerves of the eyeball determined the division of nocturnal brain metabolism into NREM and REM phases. These phases correspond to two modes of the glymphatic system - electrochemical and dynamic. The former is responsible for relaxation processes of synaptic plasticity and chemical neutralization of toxins involving water and melatonin. Rapid eye movements and increased cerebral blood flow in the second mode enhance water exchange in the parenchyma and washout of toxins into the venous system. The electrophysics of clearance and conductivity of ion and water channels of blood vessel and astrocyte membranes are modulated by oscillations of polarization potentials of water dipole domains in the plasma wall layers of arterioles and capillaries

К РАЗРАБОТКЕ ТЕСТА ДЛЯ ЭКСПРЕСС-ВЫЯВЛЕНИЯ ПРИЗНАКОВ ЛЕВШЕСТВА (ТЭВПЛ)

Article

Oct 2023

Введение: быстрое и качественное выявление левшества может быть весьма информативным в педагогике, профотборе, медицине. Для этого необходима разработка теста, который должен быть информативным, простым, кратким, быстрым в проведении и обсчете, не требующим специального оборудования. Сочетая простые вопросы и пробы, он должен выявлять стойкие и однозначные проявления левшества в разных аспектах: биографическом, моторном, сенсорном, психическом. Цель исследования: разработка универсального теста, обеспечивающего надежное и быстрое выявление признаков левшества у здоровых и больных испытуемых. Материалы и методы: по разработанному протоколу выявления левшества, состоящему из 13 вопросов и проб, обследовано 210 человек, в том числе, 100 здоровых и 110 пациентов, случайным образом выбранных во время нейропсихиатрических осмотров или нейропсихологических тестирований. Результаты: выполнение теста и заполнение протокола было быстрым, легко доступным, как при исследовании здоровых испытуемых, так и пациентов. При апробации первичного протокола обнаружено, что: а) пациенты старше 30 лет реже сообщали о наличии у себя признаков левшества, большинство из них предпочитали правую руку; б) женщины по сравнению с мужчинами чаще сообщали о наличии таких вероятных проявлений психического левшества, как вещие сны и другие варианты предвидения; в) семейное левшество чаще обнаруживалось у пациентов в сравнении со здоровыми; г) по большинству изученных показателей (7 из 13) проявления левшества чаще отмечались у пациентов с функциональными психическими заболеваниями; д) значимые корреляции обнаружены между биографическим левшеством и леворукостью, а также между леворукостью и левшеством по уху. На основании проведенного исследования создан новый усовершенствованный протокол теста экспресс-выявления признаков левшества (ТЭВПЛ). Заключение: Разработанный в результате настоящей работы модифицированный протокол ТЭВПЛ готов к использованию в дальнейших исследованиях различных контингентов здоровых и пациентов с различной психопатологической симптоматикой. Introduction: fast and high-quality detection of leftyness can be very informative in pedagogy, professional selection, medicine. To do this, it is necessary to develop a test that should be informative, simple, concise, quick to conduct and calculate, not requiring special equipment, combining simple questions and tasks, revealing mainly persistent and unambiguous signs of leftyness in various aspects such as biographical, motor, sensory, mental ones. Goal: to develop a universal test that provides reliable and fast detection of leftyness signs in healthy persons and patients. Materials and methods: according to the developed protocol for leftyness detecting, consisting of 13 questions and samples, 210 people were studied, including 100 healthy persons and 110 patients randomly selected during neuropsychiatric or neuropsychological examination. Results: test providing and protocol completion were fast, easily accessible both in the study of healthy and patients. When testing the primary protocol, it was found that: a) patients older than 30 years were less likely to report the presence of signs of leftyness, most of them preferred the right hand; b) women, compared with men, were more likely to report the presence of such mental signs of leftyness as prophetic dreams and other variants of foresight; c) familial leftyness was more often found in patients compared with healthy persons d) according to most of the studied signessigns (7 out of 13), the largest proportion of patients with leftyness was found in patients with functional mental disorders; e) significant correlations were found between biographical leftyness and left-handedness, as well as between left-handedness and ear leftyness. Based on the conducted research, a new improved protocol of test for the express detection of leftyness signs (TEDLS) was created. Conclusion: The modified TEDLS protocol developed as a result of this work is ready for use in further studies of various contingents of healthy persons and patients with various psychopathological symptoms. Key words: functional asymmetry, leftyness, left-handedness, testing

Connection of brain glymphatic system with circadian rhythm

Preprint

Full-text available

Aug 2023

Alexander Kholmanskiy

To establish the relationship between the glymphatic system of the brain and the circadian rhythm, we analyzed the effect of anomalies in water thermodynamics on the dependence of the dynamic, electrical, and optical characteristics of physiological fluids on temperature. The dynamics of hydrogen bonds in bulk and hydrated water affected the activation energies of ion currents of voltage-dependent channels that regulate signaling and trophic bonds in the neuropil of the cortical parenchyma. The physics of minimizing the of the isobaric heat capacity of water made it possible to explain the stabilization and functional optimization of the thermodynamics of eyeball fluids at 34.5 °C and the human brain during sleep at 36.5 °C. At these temperatures, the thermoreceptors of the cornea and the cells of the ganglionic layer of the retina, through connections with the suprachiasmatic nucleus and the pineal gland, switch the circadian rhythm from daytime to nighttime. The phylogenesis of the circadian rhythm was reflected in the dependence of the duration of the nighttime sleep of mammals on the diameter of the eyeball and the mass of the pineal gland. The activity of all the nerves of the eyeball led to the division of the nocturnal brain metabolism into NREM and REM phases. These phases correspond to two modes of the glymphatic system electrochemical and dynamic. The first is responsible for the relaxation processes of synaptic plasticity and chemical neutralization of toxins with the participation of water and melatonin. Rapid eye movement and an increase in cerebral blood flow in the second mode increase water exchange in the parenchyma and flush out toxins into the venous system. Electrophysics of clearance and conductivity of ionic and water channels of membranes of blood vessels and astrocytes modulate oscillations of polarization potentials of water dipole domains in parietal plasma layers of arterioles and capillaries.

Role of water in physics of blood and cerebrospinal fluid

Preprint

Full-text available

Aug 2023

Alexander Kholmanskiy

Known physical mechanisms of temperature dependence anomalies of water properties were used to explain the regularities in temperature dependence (TDs) of dynamic, electrical and optical characteristics of biological systems. The dynamics of hydrogen bonds in bulk and hydrated water affected the activation energies TDs of ion currents of voltage-dependent channels that regulate signaling and trophic bonds in the neuropil of the cortical parenchyma. The physics of minimizing the TD of the isobaric heat capacity of water made it possible to explain the stabilization and functional optimization of the thermodynamics of eyeball fluids at 34.5 C and the human brain during sleep at 36.5 C. At these temperatures, the thermoreceptors of the cornea and the cells of the ganglionic layer of the retina, through connections with the suprachiasmatic nucleus and the pineal gland, switch the circadian rhythm from daytime to nighttime. The phylogenesis of the circadian rhythm was reflected in the dependence of the duration of the nighttime sleep of mammals on the diameter of the eyeball and the mass of the pineal gland. The activity of all the nerves of the eyeball led to the division of the nocturnal brain metabolism into NREM and REM phases. These phases correspond to two modes of the glymphatic system - electrochemical and dynamic. The first is responsible for the relaxation processes of synaptic plasticity and chemical neutralization of toxins with the participation of water and melatonin. Rapid eye movement and an increase in cerebral blood flow in the second mode increase water exchange in the parenchyma and flush out toxins into the venous system. Electrophysics of clearance and conductivity of ionic and water channels of membranes of blood vessels and astrocytes modulate oscillations of polarization potentials of water dipole domains in parietal plasma layers of arterioles and capillaries.

In Vivo Corneal Elastography: A Topical Review of Challenges and Opportunities

Article

Full-text available

Apr 2023

Clinical measurement of corneal biomechanics can aid in the early diagnosis, progression tracking, and treatment evaluation of ocular diseases. Over the past two decades, interdisciplinary collaborations between investigators in optical engineering, analytical biomechanical modeling, and clinical research has expanded our knowledge of corneal biomechanics. These advances have led to innovations in testing methods (ex vivo, and recently, in vivo) across multiple spatial and strain scales. However, in vivo measurement of corneal biomechanics remains a long-standing challenge and is currently an active area of research. Here, we review the existing and emerging approaches for in vivo corneal biomechanics evaluation, which include corneal applanation methods, such as ocular response analyzer (ORA) and corneal visualization Scheimpflug technology (Corvis ST), Brillouin microscopy, and elastography methods, and the emerging field of optical coherence elastography (OCE). We describe the fundamental concepts, analytical methods, and current clinical status for each of these methods. Finally, we discuss open questions for the current state of in vivo biomechanics assessment techniques and requirements for wider use that will further broaden our understanding of corneal biomechanics for the detection and management of ocular diseases, and improve the safety and efficacy of future clinical practice.

An annular corneal microneedle patch for minimally invasive ophthalmic drug delivery

Article

Mar 2025

Microneedles directly penetrating into the cornea inevitably cause pain, corneal structure damage, and reduced light transmittance. In this work, a minimally invasive annular microneedle (A-MN) patch was developed avoiding direct puncture into the central cornea for ophthalmic drug delivery. The feasible mechanical strength of A-MNs was achieved by adjusting the ratio of PVP-β-CD and PVA to puncture the cornea barrier. Through effective diffusion to corneal stroma, bioavailability of hydrophilic small-molecule drugs, hydrophobic drugs, and macromolecular protein drugs through an A-MN patch was 24.36, 17.47, and 5.36 times higher than that of free drug administration. A-MNs effectively maintained light transmittance of the cornea with a light transmittance of 96.33 to 100%, which was higher than that of S-MNs. Furthermore, A-MNs effectively avoided corneal tissue and nerve damage along with the pain. The efficiency and safety of A-MNs were also examined through both an in vitro cell experiment and an in vivo animal experimental model, which showed great potential in clinical application.

Inorganic biomaterials for ocular drug delivery: A comprehensive review

Article

Feb 2025
J DRUG DELIV SCI TEC

An in vitro 3D collagen-based corneal construct with innervation using human corneal cell lines

Article

Full-text available

May 2024

Purpose To develop a 3-dimensional corneal construct suitable for in vitro studies of disease conditions and therapies. Design In vitro human corneal constructs were created using chemically crosslinked collagen and chondroitin sulfate extracellular matrix and seeded with 3 human corneal cell types (epithelial, stromal, and endothelial) together with neural cells. The neural cells were derived from hybrid neuroblastoma cells and the other cells used from immortalized human corneal cell lines. To check the feasibility and characterize the constructs, cytotoxicity, cell proliferation, histology, and protein expression studies were performed. Results Optimized culture condition permitted synchronized viability across the cell types within the construct. The construct showed a typical appearance for different cellular layers, including healthy appearing, phenotypically differentiated neurons. The expected protein expression profiles for specific cell types within the construct were confirmed with western blotting. Conclusions An in vitro corneal construct was successfully developed with maintenance of individual cell phenotypes with anatomically correct cellular loci. The construct may be useful in evaluation of specific corneal disorders and in developing different corneal disease models. Additionally, the construct can be used in evaluating drug targeting and/or penetration to individual corneal layers, testing novel therapeutics for corneal diseases, and potentially reducing the necessity for animals in corneal research at the early stages of investigation. Financial Disclosure(s) Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Evaluating the efficacy and safety of therapeutic interventions for corneal neuropathy: A systematic review

Article

Full-text available

Apr 2024
OCUL SURF

Eye Pain Caused by Epithelial Damage in the Central Cornea in Aqueous-Deficient Dry Eye

Article

Full-text available

Dec 2023

In this study, the severity of eye pain (EP) and associated objective findings were evaluated in aqueous-deficient dry eye (ADDE) patients using PainVision®, a quantitative pain-measuring device. This study involved 53 eyes of 53 ADDE patients (6 males and 47 females; mean age: 64.4 ± 13.4 [mean ± SD] years). Of those, 18 eyes of 18 patients underwent punctal occlusion, and EP and objective findings in those patients were evaluated before and after treatment. In all patients, the severity of EP as measured by PainVision® was assessed using the Pain Degree (PD). The median PD for the 53 patients was 30.6 µA/µA (interquartile range, 16.9–93.2), and the nasal and central corneal staining score and the upper lid-wiper epitheliopathy score were significantly correlated with PD (R = 0.33, 0.33, and 0.28, respectively) (all: p < 0.05). Using the least squares method, the central corneal staining score most significantly affected PD. In the 18 cases that underwent punctal occlusion, PD was significantly reduced (median PD: 24.8 to 7.1 µA/µA; p < 0.0001). Using the least squares method, the central corneal staining score and tear meniscus radius were significantly more influential as factors contributing to PD before and after treatment, and central corneal epithelial damage was the factor most associated with ADDE-related EP.

Thermo- and photoreceptors of eyes as regulators of circadian rhythm and glymphatic system

Preprint

Full-text available

Sep 2023

Alexander Kholmanskiy

The dynamics of hydrogen bonds in bulk and hydrated water affected the activation energies of temperature dependence of ion currents of voltage-dependent channels that regulate communication and trophic bonds in the neuropil of the cortical parenchyma. The physics of minimizing of isobaric heat capacity of water made it possible to explain stabilization and functional optimization of thermodynamics of eyeball fluids at 34.5 C and human brain during sleep at 36.5 C. At these temperatures, thermoreceptors of cornea and cells of ganglionic layer of the retina, through connections with suprachiasmatic nucleus and pineal gland, switch brain metabolism from daytime to nighttime modes. The phylogenesis of circadian rhythm was reflected in dependence of duration of nighttime sleep of mammals on diameter of eyeball, mass of pineal gland, and density of neurons in parenchyma of cortex. The activity of all nerves of eyeball led to division of nocturnal sleep into slow and fast phases. These phases correspond to two modes of glymphatic system - electrochemical and dynamic. The first is responsible for relaxation processes of synaptic plasticity and chemical neutralization of toxins with participation of water and melatonin. Rapid eye movement and an increase in cerebral blood flow in second mode increase water exchange in parenchyma and flush out toxins into venous system.

Chemical toxic exposures and chronic ocular pain

Article

Full-text available

Aug 2023

Chronic ocular pain is a common, debilitating chronic pain condition with significant morbidity and negative impact in patients’ quality of life. Several, diverse types of insults to the ocular surface can lead to acute, and under certain conditions to chronic ocular pain, and these include toxic irritants. Exposure of ocular surface to toxic irritants, in addition to direct tissue injury, carries the capacity to generated intense immune and neuronal responses with hyper-excitability, sensitization and chronic pain. Because, chronic ocular pain subsequent to toxic exposures is relatively unrecognized clinical entity, this brief review highlights pertinent concepts of its epidemiology, pathogenesis/pathophysiology, clinical progression, with recommendations for its clinical management that clinicians may find helpful. Suppression of pain signaling, generating neuronal sensitization, and prevention of chronicity of neuropathic pain is particularly emphasized in this respect.

Ocular surface itch and pain: key differences and similarities between the two sensations

Article

Jul 2023
CURR OPIN ALLERGY CL

Purpose of review: To review the pathophysiology and treatment of ocular itch and pain, encompassing nociceptive and neuropathic categories. Recent findings: Ocular itch and pain are sensations that arise from activation of ocular surface polymodal nerves. Nociceptive itch, commonly comorbid with ocular pain complaints, is mainly driven by a histamine-mediated type 1 hypersensitivity reaction. Beyond topical therapy, novel drug delivery systems are being explored to improve ocular residence time of nonsteroidal anti-inflammatory drugs (NSAIDs) and antihistamines. Nociceptive ocular pain can be driven by a variety of factors. Treatment focuses on addressing the causative sources of pain. Neuropathic ocular itch and pain are driven by nerve damage and dysfunction and as such, topical and oral neuromodulation have been explored as treatments. Oral neuromodulators include alpha 2 delta ligands, tricyclic antidepressants (TCAs), and low dose naltrexone. Novel therapies are being evaluated for both modalities such as difelikefalin (κ-opioid receptor agonist) for neuropathic itch and libvatrep (transient receptor potential vanilloid 1 antagonist) for neuropathic pain. Summary: Both ocular itch and pain can be driven by nociceptive and/or neuropathic mechanisms. Identifying contributors to abnormal ocular sensations is vital for precise medical care. Novel therapeutics for these conditions aim to improve patient outcomes and quality of life.

Comparison of Corneal sensitivity between Different types of contact lens wear

Article

Full-text available

Mar 2023

Aim and objective: The aim of this study is to find out corneal sensitivity difference among three types of contact lens wearer (RGP lens, hydrogel Contact lens and silicon hydrogel contact lens) and non-contact lens wearer who walks in tertiary eye care center. This study is conducted experiments in order to detect whether changes in sensitivity were also different for the different zones. Method: A prospective study was performed which include total 80 subjects were recruited in this study among them 20 subjects were non-contact lens users, 20 subjects were RGP wearer, 20 were soft hydrogel lens wearer and 20 were silicon hydrogel lens wearer presenting at Dr. D.Y. Patil Institute of Optometry and Visual Sciences, Pune, from October 2022 to February 2023. Corneal sensitivity is measured using fine wisp of cotton and data analysis was done based on distribution. Result: Using fine wisp of cotton time taken for response in the form of blinking is measured in seconds and found mean time, for non-contact lens wearer is 0.361, for silicone contact lens wearer is 0.415, for hyderogel contact lens wearer is 0.619 and for RGP contact lens wearer is 0.781. statistical analysis showed that all the experimental groups (non contact lens users, silicone hydrogel lens wearer, hydrogel contact lens wearer and RGP lens wearer) significantly differed in terms of corneal sensitivity from each other. Conclusion: The study can be concluded by saying both soft and RGP lens wear produce a similar type of corneal sensitivity loss, although the mechanism for this loss is different for the two lens types. The recovery of corneal sensitivity loss is achieved by cessation of contact lens. Introduction:

Clinical application of the Swiss Liquid Jet Aesthesiometer for corneal sensitivity measurement

Article

Apr 2023

Clinical relevance Corneal sensitivity represents an important indicator for corneal health, its innervation and hence also for ocular disease. It is therefore of great interest from a clinical and research perspective to quantify ocular surface sensation. Background The aim of this prospective cross-sectional cohort study was to clinically test the within-day and day-to-day repeatability of the new Swiss Liquid Jet Aesthesiometer, employing small droplets of isotonic saline solution for repeatability, and correlate with the Cochet–Bonnet aesthesiometer in a cohort of participants of two different age groups, based on participant feedback (psychophysical method). Methods Participants were recruited from two equally, large age groups: group A (18–30 years) and group B (50–70 years). The inclusion criteria were healthy eyes, Ocular Surface Disease Index (OSDI) ≤ 13, and no contact lens wear. Mechanical corneal sensitivity threshold measurements with means of liquid jet and Cochet–Bonnet methods were carried out twice during two visits (a total of four measurements), with a stimulus temperature equal to or slightly above the ocular surface temperature. Results Ninety participants completed the study (n = 45 per age group, average age in group A: 24.2 ± 2.94 years, group B: 58.5 ± 5.71 years). The coefficient of repeatability for the liquid jet method was 2.56 dB within visits and 3.61 between visits. For the Cochet–Bonnet method, it was 2.27 dB within visits and 4.42 dB between visits (Bland Altman with bootstrap analysis). Moderate correlation was observed between the liquid jet and the Cochet–Bonnet method (r = 0.540, p < .001, robust linear regression). Conclusions Swiss liquid jet aesthesiometry offers a new examiner independent method for corneal sensitivity measurement with acceptable repeatability and moderate correlation with the Cochet–Bonnet aesthesiometer. It offers a large stimulus pressure range of 100–1500 mbar and a precision of 1 mbar. Stimulus intensity can be tuned more precisely and much smaller sensitivity fluctuations may be potentially detected.

The Physiology of Cornea

Article

Full-text available

Dec 2022

Lokman Balyen

The cornea has important functions such as protecting the structures within the globe, contributing to the refractive power of the eye, and focusing the light rays on the retina with minimum scattering. Although the neurobiological complexity of the retina and the dynamic movement of the lens are absent in the cornea, it is one of the most critical components of the perfect visual system, thanks to its transparency. In order to provide sustainable transparency in the cornea, which is very important for visual function, it is possible with the intense metabolic activity in the cornea and the perfect operation of the balanced ion liquid pump. The cornea provides excellent vision thanks to the structure and functions necessary for its unique function to continue regularly. This review focuses on cornea and tear film structure and physiology.

Etiology of Dry Eye

Chapter

Full-text available

Feb 2023

Pushpa Rao

The scope of this chapter is to provide insights into the classification based on the significant factors causing dry eye. The etiological causes of dry eye have been classified broadly into two primary arms. The first arm, aqueous deficient dry eye (ADDE), illustrates malfunction of normal lacrimal secretion causing tear hyposecretion. ADDE is subdivided into Sjogren’s and the non-Sjogren’s syndrome. The former exclusively includes systemic autoimmune characteristics, while the latter comprises age-related disorders, genetic disorders, denervation in the lacrimal gland, and obstruction in tear secretion. The second arm, evaporative dry eye (EDE), explains the excessive loss of aqueous from the tear film despite the normal lacrimal secretion. Extrinsic EDE is with ocular surface pathology caused by vitamin A deficiency, contact lens wear, use of topical drugs with preservatives, and ocular surface diseases (allergic eye disease). The intrinsic EDE encompasses abnormalities in the meibomian lipid deficiency, low blink rate, and poor lid congruity. In brief, clinical tests to investigate the corneal epithelium integrity and the tear film have been discussed. This chapter aims to highlight the main etiologies of dry eye disease (DED) and current updates on techniques involved in diagnosing DED to help clinical practice.

Article

Nov 2022

Purpose: The aim of this prospective cross-sectional cohort study was to clinically test whether corneal sensation decreases with age, based on subject feedback (psychophysical method), and whether it correlates with general pain perception. Methods: Subjects were recruited from 2 equally large age groups: group A (18-30 years) and group B (50-70 years; n = 45 per group). The inclusion criteria were healthy eyes, Ocular Surface Disease Index ≤13, and no contact lens wear. Corneal sensitivity threshold (CST) measurements were performed twice during each of the 2 visits, with the aid of the new Swiss liquid jet esthesiometer for corneal sensitivity (SLACS) and Cochet-Bonnet (CB) esthesiometer. A general pain sensitivity score was obtained from all participants. Results: Ninety subjects completed the study (n = 45 per age group, average age in group A: 24.2 ± 2.94 years, group B: 58.5 ± 5.71 years). Statistically higher CSTs for age group B were only observed for SLACS (mean difference: 1.58 dB, P < 0.001). No correlation was observed between the pain score and the CSTs obtained with either esthesiometry method (r = 0.11, P = 0.25 for liquid jet and r=-0.076, P = 0.61 CB). Conclusions: A statistically significant decrease in corneal sensitivity was observed for the older age group with SLACS in this study, with CB however only a trend in the same direction was noted. General pain perception was not found to correlate with ocular surface sensation.

Transient Receptor Potential Channels: Important Players in Ocular Pain and Dry Eye Disease

Article

Full-text available

Sep 2022

Dry eye disease (DED) is a multifactorial disorder in which the eyes respond to minor stimuli with abnormal sensations, such as dryness, blurring, foreign body sensation, discomfort, irritation, and pain. Corneal pain, as one of DED’s main symptoms, has gained recognition due to its increasing prevalence, morbidity, and the resulting social burden. The cornea is the most innervated tissue in the body, and the maintenance of corneal integrity relies on a rich density of nociceptors, such as polymodal nociceptor neurons, cold thermoreceptor neurons, and mechano-nociceptor neurons. Their sensory responses to different stimulating forces are linked to the specific expression of transient receptor potential (TRP) channels. TRP channels are a group of unique ion channels that play important roles as cellular sensors for various stimuli. These channels are nonselective cation channels with variable Ca2+ selectivity. TRP homologs are a superfamily of 28 different members that are subdivided into 7 different subfamilies based on differences in sequence homology. Many of these subtypes are expressed in the eye on both neuronal and non-neuronal cells, where they affect various stress-induced regulatory responses essential for normal vision maintenance. This article reviews the current knowledge about the expression, function, and regulation of TRPs in ocular surface tissues. We also describe their implication in DED and ocular pain. These findings contribute to evidence suggesting that drug-targeting TRP channels may be of therapeutic benefit in the clinical setting of ocular pain.

Benzalkonium chloride, a common ophthalmic preservative, compromises rat corneal cold sensitive nerve activity

Article

Aug 2022
OCUL SURF

Purpose Corneal nerves comprise the densest sensory network in the body. Dysfunction of the corneal cold sensitive neurons (CSN) is implicated in ophthalmic disorders, including Dry Eye Disease, the most common ocular surface disorder. The preservative Benzalkonium chloride (BAK) and the mydriatic agent Phenylephrine hydrochloride (PHE) are considered to be inactive at the level of the CSNs. The purpose of this study is to test the impacts of continuous exposures to BAK or PHE at their clinically used concentrations on corneal nerve structure and function. Methods In vivo extracellular electrophysiology of the rat trigeminal ganglion was used to monitor CSN functional response to stimuli mimicking physiological states and stressors of the cornea. Corneal nerve structure was evaluated by immunostaining. Results Among the tested stimuli, cold probe receptive field stimulation and hyperosmolar stress were the most sensitive methods of detecting activity changes. CSN activity was attenuated after 30 min exposure to either PHE or BAK. After an hour-long washout period, BAK-treated neurons failed to recover activity while PHE-treated neurons showed signs of functional recovery. Intraepithelial nerve density was reduced and nerve fragmentation was increased in BAK-treated corneas, while PHE exposure left corneal nerves structurally intact. Conclusions Our study suggests that prolonged ocular instillations of BAK or PHE alter CSN activity through two different processes — irreversible neuronal damage in the case of BAK vs. reversible attenuation in the case of PHE.

Corneal nerves and their role in dry eye pathophysiology

Article

Jul 2022
EXP EYE RES

As the cornea is densely innervated, its nerves are integral not only to its structure but also to its pathophysiology. Corneal integrity depends on a protective tear film that is maintained by corneal sensation and the reflex arcs that control tearing and blinking. Furthermore, corneal nerves promote epithelial growth and local immunoregulation. Thus, corneal nerves constitute pillars of ocular surface homeostasis. Conversely, the abnormal tear film in dry eye favors corneal epithelial and nerve damage. The ensuing corneal nerve dysfunction contributes to dry eye progression, ocular pain and discomfort, and other neuropathic symptoms. Recent evidence from clinical studies and animal models highlight the significant but often overlooked neural dimension of dry eye pathophysiology. Herein, we review the anatomy and physiology of corneal nerves before exploring their role in the mechanisms of dry eye disease.

An Experimental Model of Neuro–Immune Interactions in the Eye: Corneal Sensory Nerves and Resident Dendritic Cells

Article

Full-text available

Mar 2022
INT J MOL SCI

The cornea is an avascular connective tissue that is crucial, not only as the primary barrier of the eye but also as a proper transparent refractive structure. Corneal transparency is necessary for vision and is the result of several factors, including its highly organized structure, the physiology of its few cellular components, the lack of myelinated nerves (although it is extremely innervated), the tightly controlled hydration state, and the absence of blood and lymphatic vessels in healthy conditions, among others. The avascular, immune-privileged tissue of the cornea is an ideal model to study the interactions between its well-characterized and dense sensory nerves (easily accessible for both focal electrophysiological recording and morphological studies) and the low number of resident immune cell types, distinguished from those cells migrating from blood vessels. This paper presents an overview of the corneal structure and innervation, the resident dendritic cell (DC) subpopulations present in the cornea, their distribution in relation to corneal nerves, and their role in ocular inflammatory diseases. A mouse model in which sensory axons are constitutively labeled with tdTomato and DCs with green fluorescent protein (GFP) allows further analysis of the neuro-immune crosstalk under inflammatory and steady-state conditions of the eye.

Working principle and relevant physical properties of the Swiss Liquid Jet Aesthesiometer for Corneal Sensitivity (SLACS) evaluation

Article

Full-text available

Feb 2022

Purpose: To describe and evaluate relevant physical properties of the Swiss Liquid Jet Aesthesiometer for Corneal Sensitivity (SLACS) for ocular surface sensitivity measurement. Methods: Characteristics of Liquid Jet (LJ) droplets (consisting of isotonic saline solution) were analysed: vertical and horizontal displacement and speed of LJ droplets were recorded with the aid of the High Speed Photron FASTCAM NOVA S6 camera (stimulus duration: 40 ms). Stimulus mass was assessed for 20 sets of 10 LJs with aid of a microbalance (pressure range of 100-1500 mbar). Results: Because continuous flow LJ disintegrated into droplets in the lower pressure range (<700 mbar), pulsed stimuli were applied in order to obtain similar stimulus characteristics across the applied pressure range. For all measurements, very little variability was observed. Vertical and horizontal displacement did not exceed 0.13 mm in either direction. The mass per shot showed an unexpected cubic dependency on pressure. Up to approximately 700 mbar, LJ speed showed an almost linear relationship. For the pressure range of >700-1500 mbar, variability increased and speed decreased compared to the expected in a linear manner. However, this may be caused by the difficulty of identifying pattern changes of LJ droplets from one high speed image frame to the next with increasing stimulus speed, when determining LJ speed via pixel count. Conclusions: Swiss Liquid Jet Aesthesiometer for Corneal Sensitivity was shown to deliver fine droplets with a pulsed stimulus mode, in a repeatable manner with precise localisation to the ocular surface. Very little variability was observed in LJ speed and mass for the typical pressure range required for clinical sensitivity measurements.

The impact of sensory neuropathy and inflammation on epithelial wound healing in diabetic corneas

Article

Jan 2022
PROG RETIN EYE RES

Diabetic peripheral neuropathy (DPN) is the most common complication of diabetes, with several underlying pathophysiological mechanisms, some of which are still uncertain. The cornea is an avascular tissue and sensitive to hyperglycemia, resulting in several diabetic corneal complications including delayed epithelial wound healing, recurrent erosions, neuropathy, loss of sensitivity, and tear film changes. The manifestation of DPN in the cornea is referred to as diabetic neurotrophic keratopathy (DNK). Recent studies have revealed that disturbed epithelial-neural-immune cell interactions are a major cause of DNK. The epithelium is supplied by a dense network of sensory nerve endings and dendritic cell processes, and it secretes growth/neurotrophic factors and cytokines to nourish these neighboring cells. In turn, sensory nerve endings release neuropeptides to suppress inflammation and promote epithelial wound healing, while resident immune cells provide neurotrophic and growth factors to support neuronal and epithelial cells, respectively. Diabetes greatly perturbs these interdependencies, resulting in suppressed epithelial proliferation, sensory neuropathy, and a decreased density of dendritic cells. Clinically, this results in a markedly delayed wound healing and impaired sensory nerve regeneration in response to insult and injury. Current treatments for DPN and DNK largely focus on managing the severe complications of the disease. Cell-based therapies hold promise for providing more effective treatment for diabetic keratopathy and corneal ulcers.

The Clinical Guiding Role of the Distribution of Corneal Nerves in the Selection of Incision for Penetrating Corneal Surgery in Canines

Article

Full-text available

Dec 2021

The cornea is one of the regions with the highest density of nerve terminals in the animal body and it bears such functions as nourishing the cornea and maintaining corneal sensation. In veterinary clinical practice, the corneoscleral limbus incision is frequently applied in cataract surgery, peripheral iridectomy, and other procedures for glaucoma. Inevitably, it would cause damage to the nerve roots that enter the cornea from the corneal limbus, thus inducing a series of complications. In this paper, the in vitro cornea (39 corneas from 23 canines, with ages ranging from 8 months old to 3 years old, including 12 male canines and 11 female canines) was divided into 6 zones, and the whole cornea was stained with gold chloride. After staining, corneal nerves formed neural networks at different levels of cornea. There was no significant difference in the number of nerve roots at the corneoscleral limbus between different zones (F = 1.983, p = 0.082), and the nerve roots at the corneoscleral limbus (mean value, 24.43; 95% CI, 23.43–25.42) were evenly distributed. Additionally, there was no significant difference in the number of corneal nerve roots between male and female canines (p = 0.143). There was also no significant difference in the number of corneal nerve roots between adult canines and puppies (p = 0.324). The results of the above analysis will provide a reasonable anatomical basis for selecting the incision location and orientation of penetrating surgery for the canine cornea in veterinary practice.

Development and Characterization of Nanoemulsions for Ophthalmic Applications: Role of Cationic Surfactants

Article

Full-text available

Dec 2021

The eye is a very complex organ comprising several physiological and physical barriers that compromise drug absorption into deeper layers. Nanoemulsions are promising delivery systems to be used in ocular drug delivery due to their innumerous advantages, such as high retention time onto the site of application and the modified release profile of loaded drugs, thereby contributing to increasing the bioavailability of drugs for the treatment of eye diseases, in particular those affecting the posterior segment. In this review, we address the main factors that govern the development of a suitable nanoemulsion formulation for eye administration to increase the patient’s compliance to the treatment. Appropriate lipid composition and type of surfactants (with a special emphasis on cationic compounds) are discussed, together with manufacturing techniques and characterization methods that are instrumental for the development of appropriate ophthalmic nanoemulsions.

Modélisation in vitro des effets de toxiques environnementaux responsables de sécheresse oculaire, sur des cellules épithéliales et des neurones sensoriels trigéminés

Thesis

Feb 2020

Michael-Adrien Vitoux

Les épithéliums de la surface oculaire sont en première ligne pour protéger l'œil des agressions extérieures, notamment des environnements aujourd’hui de plus en plus pollués et toxiques responsables de l’augmentation de l’incidence de la sécheresse oculaire. La cornée et la conjonctive, innervées par les neurones du ganglion trigéminé vont répondre à ces agressions par la mise en place de processus inflammatoires et nociceptifs. Parmi les polluants auxquels nous sommes le plus exposés se trouvent le formaldéhyde gazeux (FA) et le chlorure de benzalkonium (BAK). Nous avons testé in vitro les effets toxiques de ces deux xénobiotiques sur des cellules épithéliales cornéennes et conjonctivales et sur des neurones trigéminés. Dans une première étude, nous avons cultivé en interface air-liquide, des cellules épithéliales conjonctivales humaines de la lignée WKD afin de pouvoir les exposer à un flux de FA modélisant un stress toxique. Dans une deuxième étude, nous avons évalué les interactions entre cellules épithéliales et neurones trigéminés suite à un stress toxique. Ainsi, une culture primaire de neurones trigéminés a été exposée à un milieu conditionné (CM) produit par des cellules épithéliales cornéennes de la lignée HCE préalablement exposées à du BAK. Dans une troisième étude, nous avons développé un modèle de compartimentalisation en microfluidique des neurones trigéminés, afin d'étudier les réponses neuronales lors d’un stress toxique au BAK appliqué au niveau des terminaisons axonales. Ainsi, l’ensemble de nos résultats met en exergue des mécanismes cellulaires et moléculaires mis en jeu lors d'un stress toxique sur la surface oculaire.

Séquelles neurosensorielles post-traumatiques

Article

Nov 2017

Kératopathie neurotrophique

Article

Jun 2019

Corneal Epithelium: Cell Biology and Basic Science

Chapter

Jan 2024

Corneal Nerve and Keratocyte Response to SMILE® Surgery

Chapter

Dec 2024

Any kind of laser corneal refractive surgery has an impact on the ocular surface and corneal innervation and, therefore, on the postoperative symptoms and quality of life of patients. Minimizing the aforementioned rare, but possible, side effects, represents one of the main goals of modern laser surgery. It is claimed that small incision lenticule extraction (SMILE) induces less dry eye and wound healing phenomena as compared with laser-assisted in situ keratomileusis (LASIK) and other excimer laser-based techniques. In this chapter, the fundamentals and updates on corneal neural and keratocytes response to femtosecond lenticule extraction surgery are presented.

Corneal Nerve Anatomy

Chapter

Jan 2024

Photorefractive Keratectomy: Technical Evolution, Refractive Outcomes, Corneal Wound Healing Response, and Complications

Article

Oct 2024

Photorefractive keratectomy (PRK) was the first excimer laser procedure developed to treat refractive errors. The safety and efficacy of PRK established it as one of the most performed corneal refractive procedures worldwide. With the introduction of laser in situ keratomileusis (LASIK), and more recently keratorefractive lenticule extraction (KLEx) procedures, many corneal surgeons favor these newer corneal procedures as the first choice due to faster visual rehabilitation and less discomfort during the early postoperative period. Importantly, however, PRK remains a viable alternative for most corneal refractive candidates and there are many situations in which PRK remains the refractive procedure of choice. This review addresses the technical evolution of PRK—mechanical epithelial debridement versus alcohol-assisted epithelial removal versus excimer laser-assisted epithelial debridement (transepithelial) PRK—and reports the PRK refractive outcomes compared to other keratorefractive laser procedures. The corneal wound response associated with each PRK technique and the indications, limitations, and complications of PRK are reviewed to aid refractive surgeons to best position PRK in their overall practice. [ J Refract Surg . 2024;40(10):e754–e767.]

Corneal Development

Chapter

Jan 2024

Impact of Obesity and Age on Mouse Corneal Innervation at the Epithelial-Stromal Interface

Article

May 2024

Purpose The corneal epithelium is the most highly innervated structure in the body. Previously, we reported a novel event whereby stromal axons fuse with basal epithelial cells, limiting nerve penetration into the epithelium. Although corneal–epithelial nerves undergo changes in sensitivity and distribution throughout life and in response to an obesogenic diet, it is unknown if neuronal–epithelial cell fusion is altered. Here, we sought to determine if neuronal–epithelial cell fusion frequency correlates with obesogenic diet consumption and age. Methods Corneas were collected from C57BL/6 mice and evaluated for neuronal–epithelial cell fusion frequency using serial block-face scanning electron microscopy. To assess the correlation between diet-induced obesity and fusion frequency, 6-week-old mice were fed either a normal diet or an obesogenic diet for 10 weeks. To assess changes in fusion frequency between young and adult mice under normal dietary conditions, 9- and 24-week-old mice were used. Results Mice fed a 10-week obesogenic diet showed 87% of central-cornea stromal nerves engaged in fusion compared with only 54% in age-matched controls (16 weeks old). In 9-week-old normal-diet animals, 48% of central-cornea stromal nerves contained fusing axons and increased to 81% at 24 weeks of age. Corneal sensitivity loss correlated with increased body weight and adiposity regardless of age and diet. Conclusions Neuronal–epithelial cell fusion positively correlates with age and obesogenic diet consumption, and corneal nerve sensitivity loss correlates with increased body weight and adiposity, regardless of age and diet. As such, neuronal–epithelial cell fusion may play a role in corneal nerve density and sensitivity regulation.

Modulating Growth Factor Receptor Signaling to Promote Corneal Epithelial Homeostasis

Article

Full-text available

Nov 2023

The corneal epithelium is the first anatomical barrier between the environment and the cornea; it is critical for proper light refraction onto the retina and prevents pathogens (e.g., bacteria, viruses) from entering the immune-privileged eye. Trauma to the highly innervated corneal epithelium is extremely painful and if not resolved quickly or properly, can lead to infection and ultimately blindness. The healthy eye produces its own growth factors and is continuously bathed in tear fluid that contains these proteins and other nutrients to maintain the rapid turnover and homeostasis of the ocular surface. In this article, we review the roles of growth factors in corneal epithelial homeostasis and regeneration and some of the limitations to their use therapeutically.

Norepinephrine as the Intrinsic Contributor to Contact Lens-Induced Pseudomonas aeruginosa Keratitis

Article

Full-text available

May 2023

Purpose: Contact lens wear (CLW) is one of the leading risk factors for Pseudomonas aeruginosa keratitis (PAK). However, the intrinsic factors that contribute to the high susceptibility to keratitis during CLW remain to be elucidated. CLW over an extended period can elevate corneal norepinephrine (NE) concentration. In this study, we investigated the role of NE in promoting PAK. Methods: We constructed an injury-induced PAK model and a CLW-induced PAK model to confirm the impact of NE during corneal infection. Pharmacological blockage of NE and gene knockdown mouse were used to investigate the downstream effector of NE. RNA sequencing was performed to explore the cellular alterations during NE treatment. Non-parametric Mann-Whitney U test or Kruskal-Wallis test were used to ascertain the significance (P < 0.05). Results: Supplementation of NE led to PAK even without artificial corneal injury during CLW. The effect was mediated by the β2-adrenergic receptor (β2-AR) in the corneal epithelium. The β2-AR blockage by the NE antagonist ICI118,551 (ICI) or by deleting of its encoding gene Adrb2 significantly alleviated infection during CLW. Conversely, β2-AR activation compromised the integrity of the epithelium and significantly increased the cortical plaque marker ezrin. Transcriptome analysis identified that the protective effect of ICI on the keratitis was mediated by dual-specificity phosphatases. Suramin, a Dusp5 antagonist, abrogated the protective effect of ICI. Conclusions: These data reveal a new mechanism by which NE acts as an intrinsic factor that promotes CLW-induced PAK and provide novel therapeutic targets for treating keratitis by targeting NE-β2-AR.

Enhanced adipose derived stem cells with IGF1 modified mRNA promote wound healing following corneal injury

Article

May 2023
MOL THER

The cornea serves as an important barrier structure to the eyeball and is vulnerable to injuries, which may lead to scarring and blindness if not treated promptly. In order to explore an effective treatment that could achieve multi-dimensional repair of the injured cornea, the study herein innovatively combined modified mRNA (modRNA) technologies with adipose derived mesenchymal stem cells (ADSCs) therapy, and applied IGF-1 modRNA (modIGF1) engineered ADSCs (ADSCmodIGF1) to alkali-burned corneas in mice. The therapeutic results showed that ADSCmodIGF1 treatment could achieve the most extensive recovery of corneal morphology and function when compared not only to simple ADSCs, but also IGF1 protein eyedrops, which was reflected by the healing of corneal epithelium and limbus, the inhibition of corneal stromal fibrosis, angiogenesis and lymphangiogenesis, and also the repair of corneal nerves. In vitro experiments further proved that ADSCmodIGF1 could more significantly promote the activity of trigeminal ganglion cells and maintain the stemness of limbal stem cells than simple ADSCs, which were also essential for reconstructing corneal homeostasis. Through a combinatorial treatment regimen of cell-based therapy with mRNA technology, this study highlighted comprehensive repair in the damaged cornea and showed the outstanding application prospect in the treatment of corneal injury.

Improvement of Motor and Sensory Neuron Survival with N-acetyl cysteine after Peripheral Nerve Injury

Article

Full-text available

Nov 2018

Tahreem Fatima

Background: Nerve transfers require for the donor nerve to be injured, either partially or completely, in order to guide regenerating axons into new targets. Axon regeneration and recovery after nerve grafting and transfer may be limited by retrograde neuronal death after injury. N-acetyl cysteine (NAC) and acetyl-L-carnitine (ALC) improve survival of neurons after adult nerve injury but it is unknown whether they improve survival after paediatric or neonatal injury when neurons are most susceptible to retrograde neuronal death. Our objective is to examine whether NAC or ALC treatment improves survival of neonatal motor or sensory neurons in a rat model of neonatal nerve injury.

Wiring the ocular surface: A focus on the comparative anatomy and molecular regulation of sensory innervation of the cornea

Article

Jan 2023
DIFFERENTIATION

Tyler Schwend

The cornea is richly innervated with sensory nerves that function to detect and clear harmful debris from the surface of the eye, promote growth and survival of the corneal epithelium and hasten wound healing following ocular disease or trauma. Given their importance to eye health, the neuroanatomy of the cornea has for many years been a source of intense investigation. Resultantly, complete nerve architecture maps exist for adult human and many animal models and these maps reveal few major differences across species. Interestingly, recent work has revealed considerable variation across species in how sensory nerves are acquired during developmental innervation of the cornea. Highlighting such species-distinct key differences, but also similarities, this review provides a full, comparative anatomy analysis of sensory innervation of the cornea for all species studied to date. Further, this article comprehensively describes the molecules that have been shown to guide and direct nerves toward, into and through developing corneal tissue as the final architectural pattern of the cornea's neuroanatomy is established. Such knowledge is useful for researchers and clinicians seeking to better understand the anatomical and molecular basis of corneal nerve pathologies and to hasten neuro-regeneration following infection, trauma or surgery that damage the ocular surface and its corneal nerves.

Omega-3 polyunsaturated fatty acids and corneal nerve health: Current evidence and future directions

Article

Oct 2022
OCUL SURF

Corneal nerves play a key role in maintaining ocular surface integrity. Corneal nerve damage, from local or systemic conditions, can lead to ocular discomfort, pain, and, if poorly managed, neurotrophic keratopathy. Omega-3 polyunsaturated fatty acids (PUFAs) are essential dietary components that play a key role in neural development, maintenance, and function. Their potential application in modulating ocular and systemic inflammation has been widely reported. Omega-3 PUFAs and their metabolites also have neuroprotective properties and can confer benefit in neurodegenerative disease. Several preclinical studies have shown that topical administration of omega-3 PUFA-derived lipid mediators promote corneal nerve recovery following corneal surgery. Dietary omega-3 PUFA supplementation can also reduce corneal epithelial nerve loss and promote corneal nerve regeneration in diabetes. Omega-3 PUFAs and their lipid mediators thus show promise as therapeutic approaches to modulate corneal nerve health in ocular and systemic disease. This review discusses the role of dietary omega-3 PUFAs in maintaining ocular surface health and summarizes the possible applications of omega-3 PUFAs in the management of ocular and systemic conditions that cause corneal nerve damage. In examining the current evidence, this review also highlights relatively underexplored applications of omega-3 PUFAs in conferring neuroprotection and addresses their therapeutic potential in mediating corneal nerve regeneration.

Sensory Innervation of the Eye

Chapter

Jan 2011

Cornea and Sclera

Chapter

Jan 2011

Cornea and Sclera

Chapter

Jan 2011

The Effect of Artificial Tear Treatment on Central Corneal Thickness in Dry Eye

Article

Full-text available

Mar 2022

Ophthalmology of Lagomorpha: Rabbits, Hares, and Pikas

Chapter

Jun 2022

Joshua Seth Eaton

Members of the order Lagomorpha comprise two families, the Leporidae (domestic and wild rabbits and hares) and the Ochotonidae (pikas). There are over 60 extant species of rabbits and hares. In the wild, rabbits and hares are herbivorous, non-hibernatory, and invariably terrestrial but are found in a diversity of natural habitats on multiple continents, ranging from the subtropics to open desert to boreal forests and arctic tundra (Nowak and Walker 1999) (Table 42.1). It is noteworthy, however, that many populations of Leporidae are not native, instead introduced to their respective regions or continents by humans (Nowak and Walker 1999). The European rabbit (Oryctolagus cuniculus), for example, is not native to Australia but was introduced to the continent in the nineteenth century and has become an invasive species, reported to have a negative impact on native ecosystems (Barrio et al. 2010; Fenner 2010). The Leporidae are preyed upon by many terrestrial and avian carnivorous species, and follow predominantly crepuscular and/or nocturnal activity patterns (Delaney et al. 2018). Despite similarities in habitat and activity, social structure differs between rabbits and hares, with rabbits tending to form colonies and hares being predominantly solitary animals (Flux and Angermann 1990). At birth, rabbit kits are blind and lack fur whereas leverets (baby hares) are born with a full fur-coat and are precocial (Delaney et al. 2018).

Anesthetic Management for Ocular Interventions

Chapter

Apr 2022

Resolution of ocular procedures in horses can present several particular challenges to the anesthesia provider: many surgeries that are performed under general anesthesia require a central and immobile eye, which is best achieved by the use of neuromuscular blockers. The preocular tear film is responsible for maintaining an optically uniform ocular surface, lubricating the cornea and conjunctiva, and providing nutrients to the cornea. The aqueous humor is a transparent fluid that resembles an ultrafiltration of plasma and fills and nourishes the anterior segment structures. Anesthesia of the eye and/or surrounding structures is also necessary, in addition to sedation, for performing ocular procedures in the standing horse. A retrobulbar block is likely the most commonly used locoregional technique for achieving anesthesia of the globe. General anesthesia for ocular procedures represents a number of unique challenges. Pharmacological reversal of neuromuscular blockade is most commonly achieved with the use of acetylcholinesterase inhibitors, such as edrophonium or neostigmine.

Skin receptors in the human hand: An inference of some population properties

Article

Full-text available

Dec 1976

This chapter discusses skin mechanoreceptors in human hand. It focuses on the RA and SA I mechanosensitive units in the glabrous skin of the human hand, and the population response to localized tactile stimuli of varying amplitudes. An increase of a localized indentation has two effects: (1) a successive recruitment of units with higher thresholds at the actual point of skin indentation; in this case, the recruitment may be described on the basis of an increase of the receptive field size of the individual unit as the indentation amplitude raises; and (2) the impulse discharge in units already recruited raises. Practically all naturally occurring tactile stimuli to the human hand excite a large number of sensory units, setting up a pattern of neural activity from the population of mechanosensitive units. In addition, even the smallest variation of a suprathreshold stimulation will appreciably change this pattern.

Tactile Afferent Units with Small and Well Demarcated Receptive Fields in the Glabrous Skin Area of the Human Hand

Article

Full-text available

Jan 1979

Roland S Johansson

Microneurographic recordings have revealed that there are four distinct types of mechanoreceptive units in the glabrous skin area of the human hand (Knibestol and Vallbo, 1970; Knibestöl, 1973, 1975; Johansson, 1978). They can most readily be distinguished on the basis of their adaption to sustained skin indentation and the properties of their cutaneous receptive fields. Figure 1 gives a schematic representation of the unit types with regard to these properties. The four types, which all have thick myelinated fibers (Aa) (Knibestöl, 1973, 1975; Hagbarth, Hongell, Hallin and Torebjörk, 1970) have striking similarities to four well described types in cats and subhuman primates (Iggo, 1963; Lindblom, 1965; Lindblom and Lund, 1966; Jänig, Schmidt and Zimmermann, 1968; Talbot, Darian-Smith, Kornhuber and Mountcastle, 1968; Iggo and Muir, 1969; Chambers, Andres, Duering and Iggo, 1972; Iggo and Ogawa, 1977). The human glabrous skin units have been accordingly denoted RA, PC, SA I, and SAII (Fig. 1). These abbreviations stand for rapidly adapting, Pacinian, slowly adapting type one and slowly adapting type two, respectively.

The fine structure of the axon and growth cone of the dorsal root neuroblast of the rabbit embryo

Article

Full-text available

Jan 1970
J CELL BIOL

Virginia M. Tennyson

The centrally directed neurite of the dorsal root neuroblast has been described from the period of its initial entrance into the neural tube until a well-defined dorsal root is formed. Large numbers of microtubules, channels of agranular reticulum, and clusters of ribosomes are found throughout the length of the early axons. The filopodia of the growth cone appear as long thin processes or as broad flanges of cytoplasm having a finely filamentous matrix material and occasionally small ovoid or elongate vesicles. At first the varicosity is a small expansion of cytoplasm, usually containing channels of agranular reticulum and a few other organelles. The widely dilated cisternae of agranular reticulum frequently found within the growth cone probably correspond to the pinocytotic vacuoles seen in neurites in tissue culture. The varicosities enlarge to form bulbous masses of cytoplasm, which may measure up to 5 micro in width and 13 micro in length. They contain channels of agranular reticulum, microtubules, neurofilaments, mitochondria, heterogeneous dense bodies, and a few clusters of ribosomes. Large ovoid mitochondria having ribonucleoprotein particles in their matrix are common. Dense membrane specializations are found at the basal surface of the neuro-epithelial cell close to the area where the early neurites first enter the neural tube.

Corneal and periocular representation within the trigeminal sensory complex in the cat studied with transganglionic transport of horseradish peroxidase

Article

Full-text available

Jul 1981

The central projections of afferent fibers from the cornea, and the infraorbital, infratrochlear, frontal, lacrimal and auriculotemporal nerves were investigated by means of the transganglionic transport of horseradish peroxidase. Afferent projections to the dorsal horn of the medulla are organized along both the rostrocaudal axis and the ventrolateral to dorsomedial margin of the medullary dorsal horn. An inverted but discontinuous facial representation exists through the rostrocaudal axis of the dorsal horn of the medulla with perioral and nasal receptive fields innervated by the infraorbital and infratrochlear nerves represented rostral to the progressively more posterior receptive fields innervated by the frontal, lacrimal and auriculotemporal nerves, respectively. The organization of the primary afferents is not uniform over the laminae of the dorsal horn of the medulla; the projections from the different nerves show the least overlap in lamina II, while overlap is most extensive in laminae I and V. The sensory projection from the cornea to the medullary dorsal horn is most dense in laminae I and II. All nerves, including those innervating the cornea, project to the interpolar, oral and principal trigeminal nuclei and are somatotopically organized. Projections to the reticular formation and the contralateral trigeminal sensory complex were not found in this study. These results support the organization of the dorsal horn of the medulla proposed by Déjerine (1914) and show that this organization is most evident for the primary afferent projections to lamina II.

Trigeminothalamic neurons in nucleus caudalis responsive to tactile, thermal, and nociceptive stimulation of monkey's face

Article

Sep 1976

1. A total of 113 trigeminothalamic neurons and over 200 presumed interneurons of nucleus caudalis (0-5 mm below the obex) and subjacent reticular formation were studied in rhesus monkeys anesthetized with chloralose or nitrous oxide. Each cell was characterized in terms of its antidromic responses to stimulation of ventral posterior medial and/or posterior thalamic nuclei and to three types of stimuli applied to its receptive field: a) graded 5-s temperature shifts at a rate of 9 degrees C/s from 35 degrees C to final temperatures of 20-52 degrees C, generated by a contact thermode; b) graded intensities of electrical stimulation to determine the conduction velocities of converging primary afferent fiber populations; and c) mechanical stimulation ranging from light touch to pinch with serrated forceps. 2. This analysis yielded five classes of units distinguished by the range of responses to mechanical stimuli and by the convergence of different primary afferent fiber populations. These five classes were found among both trigeminothalamic neurons and neurons which could not be antidromically activated. Class 1 units exhibited rapidly adapting responses to hair movement or light touch and received only A-beta primary afferent input. Class 2 units responded to light touch and pressure with maintained discharges and received A-beta primary afferent input. Class 3 units responded maximally to pinch with serrated forceps but also were activated by light touch and pressure. They received A-beta, A-delta, and C fiber input. Class 4 units responded to firm pressure and maximally to pinch with serrated forceps. These units had A-delta and sometimes C fiber input. Class 5 units responded only to pinch with serrated forceps and had exclusive A-delta fiber input. Some cells in all five classes responded antidromically to stimulation of the thalamus. Antidromic action-potential latencies of classes 1,2, and 3 units were shorter than those of classes 4 and 5 units (P less than 0.001). Receptive-field sizes were usually small (1-2 cm2) for classes 1, 2, 4, and 5 units, and larger for class 3 units (one to three trigeminal divisions). The marginal layer of nucleus caudalis contained mostly classes 4 and 5 units, some class 3 units, but no classes 1 or 2 units. The superficial portion of the magnocellular layer contained mostly classes 1 and 2 units, while neurons at the base of this layer contained class 3 units and some classes 4 and 5 units. Cells in the sujacent reticular formation included all 5 classes but showed a tendency to have large receptive fields (greater than 1 trigeminal division). 3. Neurons responding to noxious thermal stimuli (44-52 degrees C) were classes 3 or 4 units. The response patterns of classes 3 and 4 units to noxious thermal stimuli were similar. No classes 1 or 2 units and only one class 5 unit responded to increases in skin temperature. Thermal thresholds ranged from 38 to 50 degrees C and most heat-responsive units responded monotonically to temperatures between 45 and 52 degrees C...

Neural regeneration following experimental wounds of the cornea in the rabbit

Article

Jan 1982

Über die Dichte und Schwellen der Schmerzpunkte der Epidermis in den verschiedenen Körperregionen

Article

H. Strughold

Ganglia of the autonomic nervous system

Article

Jan 1976

G. Gabella

Temperaturschmerz und Wärmeleitung im menschlichen Zahn

Article

Jan 1956

Etude sur l'innervation de la cornée humaine

Article

R. Martinez

Die dichte der kaltpunkte auf der haut des menschlichen korpers

Article

Ubet die topographie der warmempfindung beziehungen zwischen innervation und rezeptorischen endorganen

Article

H. Rein

The Cell and Nerves of the Human Cornea*

Article

Sep 1955
AM J OPHTHALMOL

K. Scharenberg

Pain and protopathic sensibility. A review with particular reference to the teeth

Article

Sep 1976
PAIN

Die Nerven der Hornhaut des Menschen

Article

Jan 1912

Gustavo Attias

Die Innervation der Hornhaut

Article

Nov 1961

G. Lassmann

Intensive and Extensive Aspects of Tactile Sensitivity as a Function of Body Part, Sex and Laterality

Conference Paper

Jan 1968

S Weinstein

Ciba Foundation Symposium - Touch, Heat and Pain

Chapter

May 2008

Donald Scott

ResultsReferencesDiscussion

Ein Beitrag zur Kenntnis der Nerven der Augenhäute

Article

Jan 1934

I. Ernyei

Ueber die Endigung der sensiblen Nerven in der Hornhaut

Article

Jan 1970

J. Cohnheim

Anatomical Localization of Corneal Afferent Cells in the Trigeminal Ganglion

Article

May 1978

Corneal afferent cells were identified in the trigeminal ganglion in the cat and monkey by the method of retrograde axonal transport of horseradish peroxidase. The corneal cells were found only in the ophthalmic portion of the ganglion and were scattered randomly within that division. These data are compatible with clinical and other experimental descriptions of the organization of the trigeminal ganglion and sensory root.

Neurons that subserve the sensory-discriminate aspects of pain

Article

Sep 1977

Response characteristics of corneal sensory fibers to mechanical and thermal stimulation

Article

Dec 1979
BRAIN RES

Corneal pain evoked by thermal sensation

Article

Sep 1979

The thermal sensitivity of the eyelid and cornea was compared using an automated apparatus to produce stimulus pulses of known magnitude and duration over the range 33--45 degrees C. Subjects reported only temperature sensation when the skin of the upper eyelid was tested; however, corneal stimulation in the same subjects was always perceived as nociceptive. The possibility that other ocular tissues may be involved in the pain responses was shown to be unlikely by direct experimentation or by calculation of heat flow in those tissues. Cornea and eyelid thresholds were compared in relationship to the structural and physical properties of these tissues. It was found that the nerve endings of the corneal epithelium are less sensitive to temperature change when compared to the thermal receptors of the eyelid. It is concluded that the cornea is useful for the experimental study of pain.

Pain and protopathic sensibility. A reveiw with particular reference to the teeth

Article

Oct 1976

Trigeminothalamic Neurons in Nucleus Caudalis Responsive to Tactile, Thermal, and Nociceptive Stimulation of Monkey's Face

Article

Oct 1976

[On the aesthesiometrie of the cornea (author's transl)]

Article

Nov 1976

Based especially on the studies of v. Frey, the anatomical, physiological and methodical fundamentals of aesthesiometrie of the cornea are considered and an electromagnetic instrument for the quantitative reproductable aesthesiometrie of the cornea is introduced. With this instrument it is shown by using various sizes of tactile probes, that the threshold value of the corneal sensitivity does not primarily depend on the size of the tactile probe, but mainly on the applied pressure. Moreover, the threshold of corneal sensitivity was measured at seventeen different points and a topographical description of the sensitivity conditions elaborated.

Pain from dentine and pulp

Article

Jun 1975

D J Anderson

Fine structure of nerve endings in the human dental pulp

Article

Aug 1968
ARCH ORAL BIOL

Thick sections of the peripheral coronal areas of the mature dental pulp were examined under light microscopy and thin sections prepared for electron microscopy after fixation in Palade's osmium tetroxide. The area examined corresponded to the "plexus of Raschkow" and myelinated nerve fibres 2-5 μ dia. and unmyelinated nerve fibres 2500-16,000 Å dia. were seen. Three types of nerve endings could be identified by the presence of vesicles and mitochondria within their structure. The first type, presumably derived from myelinated nerve fibres, displayed varicosities up to 4 μ dia. and constrictions of 1 μ diameter, and axonal swellings 5000-10,000 Å dia. The second type consisted of fine-diameter unmyelinated nerve fibres exposed freely in the ground substance, which presumably correspond to pain afferent terminals. The third type consisted of unmyelinated fibres related to blood vessels.

Electron microscopic study on the corneal nerve with special reference to its endings

Article

Aug 1968

H Matsuda

Corneal reflex elicited by electrical stimulation of the human cornea

Article

Aug 1980

The corneal reflex can be elicited in humans by electrical stimulation of the cornea. This method is harmless and allows precise quantification of the reflex response. In 18 patients with trigeminal lesions, the reflex was abolished or significantly altered on the diseased side in all cases. Measurement of the threshold is the most significant characteristic.

Specific sensations evoked by activity in single identified sensory units in man

Article

Jan 1981

Innervation density of mechanorecep-tive fibers supplying glabrous skin of the monkey''s index finge

Article

Jan 1981

1. The innervation densities of mechanoreceptive fibres supplying the ridged glabrous skin of the middle and terminal phalanges of the monkey's (Macaca nemestrina) index finger were estimated using a combination of histological and neurophysiological procedures. 2. This estimate was based on (a) a count of the total number of A beta myelinated fibres in the palmar digital nerve at the level of the proximal phalanx, (b) the demonstration that the majority of A beta fibres in the monkey's palmar digital nerve are mechanoreceptive afferents, (c) the estimation, based on a sample of 398 fibres, of the fractions of rapidly adapting, slowly adapting and Pacinian mechanoreceptive fibres in the palmar digital nerve, and (d) the estimation of the area of glabrous skin innervated by the palmar digital nerve. 3. The estimated innervation density of the finger pad and the skin of the middle phalanx were: rapidly adapting fibres, 178 and 80/cm2; slowly adapting fibres, 134 and 46/cm2; and Pacinian fibres, 13/cm2 for both phalanges.

Sensory experiences in man evoked by intraneural electrical stimulation of intact cutaneous afferent fibers

Article

Feb 1981

The response of slowly conducting myelinated and unmyelinated afferent units to natural types of cutaneous stimuli was recorded extracellularly with tungsten microelectrodes from intact human skin nerves. Seven fibers had characteristics of C-polymodal units (conduction velocity: 0.75–1.2 m/s) and two fit descriptions of myelinated high-threshold mechanoreceptors (conduction velocity of one: 19 m/s). Attempts were made to evoke a sensation in a subject by stimulating the impaled fascicles directly with electrical pulses of controlled amplitude, duration and frequency so as to try to correlate responsive properties of the sensory units and sensory experience. The subjective sensations evoked by natural stimuli to the skin surface were used as criteria for comparison.

Responses of cat corneal receptors to mechanical and thermal stimulation

Article

Jan 1982

1. The afferent responses evoked by mechanical and thermal stimulation of the cat cornea were recorded extracellularly from strands of long and mixed ciliary nerves under deep anaesthesia. 94% of the units studied (n = 53) responded consistently to both stimuli. 2. Conduction velocities, measured by electrical stimulation of the receptive field, corresponded to the lower range of the A-delta fibre group (average = 5.4 m/sec). Receptive fields covered approximately a quadrant of the corneal surface and showed continuous sensitivity and overlapping. Units were silent in the absence of stimulation but an ongoing activity was commonly present after repeated mechanical and thermal stimulation. 3. Mechanical responses were evoked at low thresholds and consisted of a dynamic and static response that paralleled the amplitude of the stimulus. The pattern of the discharge was irregular and fatigue was easily developed by repeated stimulation. 4. Thresholds to heating were above 38 degrees C and the response increased monotonically with the temperature over the range from threshold to 50 degrees C. The heat response could be sensitized by repeated long suprathreshold stimulation while variable changes in the response were induced by briefer stimuli. Also depression was observed in some circumstances. A weak response to cooling was present in 50% of the units tested. 5. Damaging mechanical stimulation or the application of a strong acid solution evoked a vigorous response followed by an earlier discharge that persisted for hours. 6. The relation of these receptors to other polymodal nociceptors and corneal sensation is considered.

Sensory denervation of the rabbit affects epithelial properties

Article

Aug 1980

Sensory denervation of the corneal epithelium was obtained by circumscribed lesions of the trigeminal ganglion. Two physiological effects were found: an increase in epithelial permeability and a decreased ability to repair a standardized epithelial abrasion.

Source and nature of nerve fibers in cat cornea

Article

Sep 1953
Arch Neurol Psychiatr

F C RODGER

IT IS GENERALLY accepted that the cornea is supplied entirely by pain fibers from the ophthalmic division of the trigeminus. Less well known are the various conceptions and arguments put forward as to their other sources and functions, i. e., that the maxillary division supplies the lower half of the cornea (Jefferson1), that autonomic fibers coexist with the sensory (Behr,2 Knapp,3 Dandy,4 Boeke,5 Nageotte and Guyon,6 and Marchesani7), that large multipolar nerve cells are occasionally present (Zander and Weddell8), and that, in addition to pain, the modality of touch exists (Rowbotham9; Grant, Groff, and Lewy10; Tower,11 and others).My colleagues and I undertook the experimental studies to be described here in the hope that further light might be thrown on these questions.EXPERIMENTAL INVESTIGATION Methods. —Intracranial division of the ophthalmic, maxillary, and oculomotor nerves was performed successfully on 14

Comparison of thermal sensitivity of the forehead, lip, conjunctiva and cornea

Article

Dec 1960
J Appl Physiol

D. R. Kenshalo

The cornea is innervated by bare nerve endings of greater density than skin. If these act as thermal receptors, the cornea should be more sensitive to thermal stimulation than skin because of its dense innervation, surface proximity of the nerve terminals and absence of vascular system. Comparisons were made of the thermal sensitivities of the upper lip, forehead, conjunctiva and cornea. Although no thermal sensations were obtained from the cornea by applications of temperatures ranging from 20° to 55°C, all observers reported sensation changes at certain points on the temperature continuum. These were described in terms of irritation, whereas similar temperatures applied to the other sites felt cool, warm or hot. Comparison of the cool, warm and hot thresholds of the lip, forehead and conjunctiva showed them to be generally similar (P > 0.05). Stimulus temperatures at which corneal sensations changed were significantly different (P < 0.002) from the thresholds obtained at the other test sites. It is concluded that the cornea differs both quantitatively and qualitatively in its response to thermal stimulation from the other regions tested. Note: (With the Assistance of B. P. Childers and R. Webb) Submitted on June 10, 1960

[The innervation of the cornea. Research on the resting cornea in rabbits after mild scarification, intraocular infection with Box virus bovis and bilateral sympathectomy]

Article

Feb 1961

G. Lassmann

An electron microscope study of the cornea in mice, with special reference to the innervation

Article

Aug 1960

Mary Whitear

Development changes in epidermal innervation

Article

Nov 1961

M. J. T. Fitzgerald

Observations on the innervation of the cornea

Article

Feb 1951

Diameters of Nerve Fibers in Human Tooth Pulps

Article

Sep 1951
J AM DENT ASSOC

The significance of beading in corneal nerve fibres

Article

Jan 1952

F C RODGER

The Pattern of the Corneal Innervation in Rabbits

Article

Mar 1950

F C RODGER

Continuity in Nerve Fibres.

Article

Aug 1937

H H Woollard

Sensory specialization of free nerve endings in the rabbit cornea

Jan 1981
272

Tanelian

Tanelian, D.L. and Beuerman, R.W., Sensory specialization of free nerve endings in the rabbit cornea, Neurosci. Abstr., 7 (198 1) 272.

The significance of beading in cornea1 nerve fibres Source and nature of nerve fibers in cat cornea

Jan 1951
70-206

F C Rodger

Rodger, F.C., The significance of beading in cornea1 nerve fibres, J. Physiol. (Lond.), 115 (1951) 67P. 43 Rodger, F.C., Source and nature of nerve fibers in cat cornea, Arch. Neurol. Psychiat. (Chic.), 70 (1953) 206-223.

Excitation of the dentinal receptor in the tooth of the cat

Jan 1966
261

Scott

Scott, Jr., D., Excitation of the dentinal receptor in the tooth of the cat. In: A.V.S. De Reuck and J. Knight (Eds.), Ciba Foundation Symposium on Touch, Heat, and Pain, Churchill, London, 1966, pp. 261-274.

Intensive and extensive aspects of tactile sensitivity as a function of body part, sex, and laterality The Skin Senses An electron microscope study of the cornea in mice, with special reference to the innervation

Jan 1960
195-218

S Weinstein

Weinstein, S., Intensive and extensive aspects of tactile sensitivity as a function of body part, sex, and laterality. In: D.R. Kenshalo (Ed.), The Skin Senses, Thomas. Springfield, Ill., 1968, pp. 195-218. 52 Whitear, M., An electron microscope study of the cornea in mice, with special reference to the innervation, J. Anat. (Lond.), 194 (1960) 387-409.

Density and organization of free nerve endings in the corneal epithelium of the rabbit

Abstract

No full-text available

Recommended publications

Ocular surface alterations and in vivo confocal microscopic characteristics of corneas in patients w...

[Differing regulation of proliferation of limbus and corneal epithelium caused by serum factors]

[Biochemical characteristics and cellular localization of specific antigens in the frog corneal epit...

The proliferative response during regeneration of a ringshaped defect in the corneal epithelium