Jan Provis

Jan Provis
Australian National University | ANU · ANU Medical School; JCSMR

PhD

About

174
Publications
19,249
Reads
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8,285
Citations
Citations since 2017
32 Research Items
3154 Citations
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20172018201920202021202220230100200300400500600
20172018201920202021202220230100200300400500600
Introduction
Between 2007 and 2018 I was Professor of Anatomy and Associate Dean in the Medical School at The Australian National University, and Associate Director of the ARC Centre of Excellence in Vision Science. My research work has focussed on how the macula and fovea have evolved, how they develop, the molecular factors involved, the functional constraints, and the vulnerability to degeneration. I believe that education is a right, and the only plausible way to achieve a society where all are equal.
Additional affiliations
January 2012 - May 2016
Australian National University
Position
  • Group Leader
January 2012 - May 2016
Australian National University
Position
  • Group Leader; Associate Dean (Teaching and Learning)
January 2008 - present
The Australian National University
Position
  • Professor of Anatomy / Associate Dean

Publications

Publications (174)
Article
Full-text available
Objective To assess outer retinal layer maturation during late gestation and early postnatal life using optical coherence tomography and histologic examination. Methods Thirty-nine participants 30 weeks' postmenstrual age or older were imaged using a handheld optical coherence tomography system, for a total of 102 imaging sessions. Foveal images fr...
Article
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Background The recruitment and activation of inflammatory cells is thought to exacerbate photoreceptor death in retinal degenerative conditions such as age-related macular degeneration (AMD). We investigated the role of Müller cell-derived chemokine (C-C motif) ligand (Ccl)2 expression on monocyte/microglia infiltration and photoreceptor death in l...
Article
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Objective To evaluate the safety and tolerability of a mineralocorticoid, in a single-dose intravitreal (IVT) injection of 1 mg/0.1 mL and 2 mg/0.1 mL fludrocortisone acetate (FCA) in subjects with geographical atrophy (GA) secondary to age-related macular degeneration. Methods and Analysis This phase 1b study was a two-part dose-escalation prospe...
Article
Full-text available
Background MicroRNA (miRNA) play a significant role in the pathogenesis of complex neurodegenerative diseases including age-related macular degeneration (AMD), acting as post-transcriptional gene suppressors through their association with argonaute 2 (AGO2) - a key member of the RNA Induced Silencing Complex (RISC). Identifying the retinal miRNA/mR...
Article
Full-text available
The pathogenesis of outer retinal degenerations has been linked to the elevation of cytokines that orchestrate pro-inflammatory responses within the retinal milieu, and which are thought to play a role in diseases such as geographic atrophy (GA), an advanced form of AMD. Here we sought investigate the anti-inflammatory and mechanistic properties of...
Article
Purpose: Dysregulation of the complement cascade contributes to a variety of retinal dystrophies, including age-related macular degeneration (AMD). The central component of complement, C3, is expressed in abundance by macrophages in the outer retina, and its ablation suppresses photoreceptor death in experimental photo-oxidative damage. Whether th...
Article
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Purpose: To examine the foveal avascular zone (FAZ) in patients with congenital achromatopsia (ACHM). Methods: Forty-two patients with genetically confirmed ACHM were imaged either with Optovue's AngioVue system or Zeiss's Plex Elite 9000, and the presence or absence of a FAZ was determined. For images where a FAZ was present and could be confid...
Article
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Introduction: MicroRNAs (miRNAs) are small, non-coding RNA molecules that have powerful regulatory properties, with the ability to regulate multiple messenger RNAs (mRNAs) and biological pathways. MicroRNA-223-3p (miR-223) is known to be a critical regulator of the innate immune response, and its dysregulation is thought to play a role in inflamma...
Preprint
Full-text available
MicroRNA (miRNA) play a significant role in the pathogenesis of complex neurodegenerative diseases, including age-related macular degeneration, acting as post-transcriptional gene suppressors through their association with argonaute (AGO) protein family members. However, to understand their role in disease, investigation into the regulatory nature...
Article
Purpose: The use of small non-coding nucleic acids, such as siRNA and miRNA, has allowed for a deeper understanding of gene functions, as well as for development of gene therapies for complex neurodegenerative diseases, including retinal degeneration. For effective delivery into the eye and transfection of the retina, suitable transfection methods...
Article
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Background: The role of the alternative complement pathway and its mediation by retinal microglia and macrophages, is well-established in the pathogenesis of Age-Related Macular Degeneration (AMD). However, the contribution of the classical complement pathway towards the progression of retinal degenerations is not fully understood, including the r...
Article
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Purpose: Glutathione-S-transferase omega 1-1 (GSTO1-1) is a cytosolic glutathione transferase enzyme, involved in glutathionylation, toll-like receptor signaling, and calcium channel regulation. GSTO1-1 dysregulation has been implicated in oxidative stress and inflammation, and contributes to the pathogenesis of several diseases and neurological d...
Article
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Purpose: We sought to determine the role and retinal cellular location of microRNA-124 (miR-124) in a neuroinflammatory model of retinal degeneration. Further, we explored the anti-inflammatory relationship of miR-124 with a predicted messenger RNA (mRNA) binding partner, chemokine (C-C motif) ligand 2 (Ccl2), which is crucially involved in inflam...
Article
Full-text available
The pathogenesis of many retinal degenerations, such as age-related macular degeneration (AMD), is punctuated by an ill-defined network of sterile inflammatory responses. The delineation of innate and adaptive immune milieu among the broad leukocyte infiltrate, and the gene networks, which construct these responses, are poorly described in the eye....
Article
Full-text available
The complement system is highly implicated in both the prevalence and progression of Age-Related Macular Degeneration (AMD). Complement system inhibitors therefore have potential therapeutic value in managing excessive activation of the complement pathways in retinal degenerations. The vaccinia virus complement control protein (VCP) has been shown...
Article
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Purpose Systemic increases in reactive oxygen species, and their association with inflammation, have been proposed as an underlying mechanism linking obesity and age-related macular degeneration (AMD). Studies have found increased levels of oxidative stress biomarkers and inflammatory cytokines in obese individuals; however, the correlation between...
Preprint
Full-text available
The pathogenesis of many retinal degenerations, such as age-related macular degeneration (AMD), is punctuated by an ill-defined network of sterile inflammatory responses. The delineation of innate and adaptive immune milieu amongst the broad leukocyte infiltrate, and the gene networks which construct these responses, are poorly described in the eye...
Article
Full-text available
Background Chemokine signalling is required for the homing of leukocytes during retinal inflammation, and is associated with pathogenesis of diseases such as age-related macular degeneration (AMD). Here, we explore the role of interleukin-1β (IL-1β) in modulating AMD-associated chemokines Ccl2, Cxcl1, and Cxcl10 during photo-oxidative retinal damag...
Article
Müller cells, the supporting cells of the retina, play a key role in responding to retinal stress by releasing chemokines, including CCL2, to recruit microglia and macrophages (MG/MΦ) into the damaged retina. Photobiomodulation (PBM) with 670 nm light has been shown to reduce inflammation in models of retinal degeneration. In this study, we aimed t...
Article
Full-text available
Purpose: Complement system dysregulation is strongly linked to the progression of age-related macular degeneration (AMD). Deposition of complement including C3 within the lesions in atrophic AMD is thought to contribute to lesion growth, although the contribution of local cellular sources remains unclear. We investigated the role of retinal microg...
Article
Age-related macular degeneration (AMD) is a multifactorial disorder that affects millions of individuals worldwide. While the advent of anti-VEGF therapy has allowed for effective treatment of neovascular ‘wet’ AMD, no treatments are available to mitigate the more prevalent ‘dry’ forms of the disease. A role for inflammatory processes in the progre...
Article
Purpose: Light is a requirement for the function of photoreceptors in visual processing. However, prolonged light exposure can be toxic to photoreceptors, leading to increased reactive oxygen species (ROS), lipid peroxidation, and photoreceptor cell death. We used the 661W mouse cone photoreceptor-like cell line to study the effects of pyruvate in...
Conference Paper
Purpose: Patients with age-related macular degeneration (AMD) have difficulty recognising faces and facial expressions. We examined if this could be improved using an image enhancement procedure derived from high-level cortical coding of faces in a perceptual 'face-space', namely caricaturing. Caricaturing exaggerates the ways in which the shape in...
Article
Light–induced degeneration in rodent retinas is an established model for of retinal degeneration, including the roles of oxidative stress and neuroinflammatory activity. In these models, photoreceptor death is elicited via photo-oxidative stress, and is exacerbated by recruitment of subretinal macrophages and activation of immune pathways including...
Article
Full-text available
The activity of macrophages is implicated in the progression of retinal pathologies such as atrophic age-related macular degeneration (AMD), where they accumulate among the photoreceptor layer and subretinal space. This process is aided by the local expression of chemokines, which furnish these cells with directional cues that augment their migrati...
Article
Full-text available
Photobiomodulation at a wavelength of 670 nm has been shown to be effective in preventing photoreceptor cell death in the retina. We treated Sprague-Dawley (SD) rats with varying doses of 670 nm light (9; 18; 36; 90 J/cm 2 ) before exposing them to different intensities of damaging white light (750; 1000; 1500 lux). 670 nm light exhibited a biphasi...
Article
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Background The recruitment of macrophages accompanies almost every pathogenic state of the retina, and their excessive activation in the subretinal space is thought to contribute to the progression of diseases including age-related macular degeneration. Previously, we have shown that macrophages aggregate in the outer retina following damage elicit...
Article
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Purpose: The proteomic profile of vitreous from second-trimester human embryos and young adults was characterized using mass spectrometry and analyzed for changes in protein levels that may relate to structural changes occurring during this time. This vitreous proteome was compared to previous reports to confirm proteins already identified and rev...
Article
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Purpose:To investigate the expression profile of and identify all miRNAs that potentially regulate inflammation in a light-induced model of focal retinal degeneration. Methods:Sprague Dawley (SD) rats aged 90-140 post-natal days were exposed to 1000 lux white fluorescent light for 24 hours. At 24 hours and 3, 7 days post exposure the animals were e...
Article
Objective: Retinopathy of prematurity (ROP) is a vasoproliferative disorder of the retina affecting extremely preterm or low birth weight infants The aim of this study was to assess the feasibility and safety of 670 nm red light use in a neonatal intensive care unit. Study design: Neonates <30 weeks gestation and <1150 g were enrolled within 48...
Article
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Background Monocyte infiltration is involved in the pathogenesis of many retinal degenerative conditions. This process traditionally depends on local expression of chemokines, though the roles of many of these in the degenerating retina are unclear. Here, we investigate expression and in situ localization of the broad chemokine response in a light-...
Article
Resident microglial cells can be regarded as the immunological watchdogs of the brain and the retina. They are active sensors of their neuronal microenvironment and rapidly respond to various insults with a morphological and functional transformation into reactive phagocytes. There is strong evidence from animal models and in situ analyses of human...
Chapter
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The fetal hyaloid vasculature plays a critical role in many aspects of proper ocular development. The hyaloid artery (HA) is a large vessel that extends from the optic disc through the vitreous where it branches and extends to the posterior surface of the lens to anastamose with the tunica vasculosa lentis (TVL) which supplies nutrients to the deve...
Chapter
Vitreous is a highly hydrated, avascular extracellular matrix located between the lens and retina that serves a variety of structural and physiological functions [1, 2]. Formation of the vitreous is a complex process that has been studied for over a century and still is not clearly understood. Two overlapping developmental phases have been describe...
Article
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Red/near-infrared irradiation therapy (R/NIR-IT) delivered by laser or light-emitting diode (LED) has improved functional outcomes in a range of CNS injuries. However, translation of R/NIR-IT to the clinic for treatment of neurotrauma has been hampered by lack of comparative information regarding the degree of penetration of the delivered irradiati...
Article
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The morphological characterization of quasi-planar structures represented by gray-scale images is challenging when object identification is sub-optimal due to registration artifacts. We propose two alternative procedures that enhances object identification in the integral-geometry morphological image analysis (MIA) framework. The first variant stre...
Article
Full-text available
Complement activation is thought to contribute to the pathogenesis of age-related macular degeneration (AMD), which may be mediated in part by para-inflammatory processes. We aimed to investigate the expression and localization of C3, a crucial component of the complement system, in the retina during the course of aging. SD rats were born and reare...
Article
Full-text available
Damage to central vision, of which age-related macular degeneration (AMD) is the most common cause, leaves patients with only blurred peripheral vision. Previous approaches to improving face recognition in AMD have employed image manipulations designed to enhance early-stage visual processing (e.g., magnification, increased HSF contrast). Here, we...
Article
Full-text available
Irradiation with light wavelengths from the far red (FR) to the near infrared (NIR) spectrum (600 nm -1000 nm) has been shown to have beneficial effects in several disease models. In this study, we aim to examine whether 670 nm red light pretreatment can provide protection against hyperoxia-induced damage in the C57BL/6 J mouse retina. Adult mice (...
Article
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To investigate the validity of using 670nm red light as a preventative treatment for Retinopathy of Prematurity in two animal models of oxygen-induced retinopathy (OIR). During and post exposure to hyperoxia, C57BL/6J mice or Sprague-Dawley rats were exposed to 670nm light for 3 minutes a day (9J/cm(2)). Whole mounted retinas were investigated for...
Article
Age-related macular degeneration (AMD) damages central vision, leaving only blurred peripheral vision. This severely impacts face recognition and thus social functioning. Here, we explore whether face recognition could be improved in AMD, by manipulating the physical face image such that it better suits the perceptual mechanisms humans use to recog...
Article
Full-text available
Abstract Irradiation in the red/near-infrared spectrum (R/NIR, 630-1000 nm) has been used to treat a wide range of clinical conditions, including disorders of the central nervous system (CNS), with several clinical trials currently underway for stroke and macular degeneration. However, R/NIR irradiation therapy (R/NIR-IT) has not been widely adopte...
Article
Retinopathy of prematurity (ROP) is a vasoproliferative disorder that can lead to blindness. Red light irradiation at 670 nm wavelength promotes cellular differentiation, proliferation and wound repair. 670 nm light is believed to stimulate mitochondrial function by increasing cytochrome oxidase efficiency and ATP production. In the retina, 670 nm...
Article
Full-text available
Irradiation in the red/near-infrared spectrum (R/NIR, 630-1000 nm) has been used to treat a wide range of clinical conditions, including disorders of the central nervous system (CNS), with several clinical trials currently underway for stroke and macular degeneration. However, R/NIR irradiation therapy (R/NIR-IT) has not been widely adopted in clin...
Article
Full-text available
Aim Complement activation is associated with the pathogenesis of age-related macular degeneration (AMD). We aimed to investigate whether 670-nm light treatment reduces the propagation of complement in a light-induced model of atrophic AMD. Methods Sprague–Dawley (SD) rats were pretreated with 9 J/cm2 670-nm light for 3 minutes daily over 5 days; o...
Article
Our aim is to investigate a common role of the complement system in the pathogenesis of retinal disease, by assessing the expression profile of complement component 3 (C3) in three mechanistically distinct models of retinal degeneration: light-damage, hyperoxia and the degenerative P23H-3 rodent strain. In the light damage model, young adult albino...
Article
How does the number of motor neurons in the brain correlate with the muscle mass to be controlled in the body? Numbers of motor neurons are known to be adjusted during development by cell death, but the change in the percentage of surviving motor neurons in response to experimental changes in target muscle mass is relatively small. Here we address...
Article
Background Retinopathy of prematurity is a vasoproliferative disorder that can cause blindness and adverse visual outcomes in extremely premature neonates. Red light at 670nm wavelength promotes cellular differentiation, proliferation and wound repair. Aims To determine whether 670nm light promotes normal retinal vessel development in a mouse model...