Pedro Lax

• Professor
• University of Alicante

Flow cytometry enables the detection and characterization of specific cell populations, and proper identification of particular cell types can be assessed by immunohistochemistry. Here, we describe the identification and sorting of nonhematopoietic stem cells expressing stem cell antigen-1 from adult murine retinas using flow cytometry and immunohi...

Purpose: This study assessed retinal cells in the macula of human donors with diabetes with or without retinopathy. Methods: Seventeen human donor retinas were classified as diabetes mellitus (DM, n = 7), diabetes with diabetic retinopathy (DR, n = 3), or control (n = 8). Macular transversal sections were analyzed for photoreceptors, bipolar cel...

Purpose: Central Areolar Choroidal Dystrophy (CACD) is a monogenic hereditary retinal disorder characterized by progressive retinal degeneration. In most cases, CACD presents an autosomal dominant inheritance pattern in which patients carry a single mutation in the peripherin (PRPRH2) gene. This study presents a functional, immunohistochemical and...

Aims/Purpose: Inherited retinal dystrophies (IRD) are retinal neurodegenerations that course with photoreceptor cell death and neuroinflammation. Microglia, astrocytes and Müller cells are the main glial cells involved in retinal neuroinflammation, but its role is still not fully understood. These cells show evidence of both beneficial and harmful...

Aims/Purpose: Central areolar choroidal dystrophy (CACD) is a rare hereditary disease that leads to progressive retinal and choriocapillaris degeneration and vision loss. In Spain, there is a family suffering this disease, since they carry the mutation p.Arg195Leu in PRPH2 . Our team have generated a mouse model of CACD carrying the same mutation a...

The mammal retina does not have the capacity to regenerate throughout life, although some stem and progenitor cells persist in the adult retina and might retain multipotentiality, as previously described in many tissues. In this work we demonstrate the presence of a small lineage− Sca-1+ cell population in the adult mouse retina which expresses fun...

Ischemia is the main cause of cell death in retinal diseases such as vascular occlusions, diabetic retinopathy, glaucoma, or retinopathy of prematurity. Although excitotoxicity is considered the primary mechanism of cell death during an ischemic event, antagonists of glutamatergic receptors have been unsuccessful in clinical trials with patients su...

Central areolar choroidal dystrophy is an inherited disorder characterized by progressive choriocapillaris atrophy and retinal degeneration and is usually associated with mutations in the PRPH2 gene. We aimed to generate and characterize a mouse model with the p.Arg195Leu mutation previously described in patients. Heterozygous ( Prph2 WT/KI ) and h...

Purpose Central areolar choroidal dystrophy is an inherited disorder characterized by progressive choriocapillaris atrophy and retinal degeneration, usually associated with mutations in the PRPH2 gene. We aimed to generate and characterize a mouse model with the p.Arg195Leu mutation previously described in patients. Methods Heterozygous (Prph2WT/KI...

Background The main clinical symptoms characteristic of Parkinson’s disease (PD) are bradykinesia, tremor, and other motor deficits. However, non-motor symptoms, such as visual disturbances, can be identified at early stages of the disease. One of these symptoms is the impairment of visual motion perception. Hence, we sought to determine if the sta...

Background: Different ocular alterations have been described in patients with coronavirus disease 2019 (COVID-19). Our aim was to determine whether COVID-19 affected retinal cells and establish correlations with clinical parameters. Methods: Retinal sections and flat-mount retinas from human donors with COVID-19 (n = 16) and controls (n = 15) we...

The purinergic receptor P2X7 (P2X7R) is implicated in all neurodegenerative diseases of the central nervous system. It is also involved in the retinal degeneration associated with glaucoma, age-related macular degeneration, and diabetic retinopathy, and its overexpression in the retina is evident in these disorders. Retinitis pigmentosa is a progre...

Multiple gene mutations have been associated with inherited retinal dystrophies (IRDs). Despite the spectrum of phenotypes caused by the distinct mutations, IRDs display common physiopathology features. Cell death is accompanied by inflammation and oxidative stress. The vertebrate retina has several attributes that make this tissue vulnerable to ox...

Inherited retinal dystrophies (IRDs) are a large group of genetically and clinically heterogeneous diseases characterized by the progressive degeneration of the retina, ultimately leading to loss of visual function. Oxidative stress and inflammation play fundamental roles in the physiopathology of these diseases. Photoreceptor cell death induces an...

Purpose: To assess the changes in retinal morphology in a rat model of chronic glaucoma induced by ocular hypertension. Methods: Intraocular pressure (IOP) was surgically increased through weekly injections of sodium hyaluronate (HYA) in the anterior eye chamber of the left eye of male Wistar rats, whereas the right eyes were sham operated (salt...

This review focuses on retina degeneration occurring during glaucoma, age-related macular degeneration (AMD), diabetic retinopathy (DR), and retinitis pigmentosa (RP), and on the potential therapeutic use of triads of repositioned medicines, addressed to distinct but complementary targets, to prevent, delay or stop retina cell death. Although myria...

Purpose Retinitis pigmentosa is primarily characterized by a massive photoreceptor loss. But a global retinal remodeling occurs in later stages of the disease. At that phase, glial cells and retinal vasculature are also strongly affected. The main aim of the present work is to assess if the bile acid Tauroursodeoxicholic acid (TUDCA), which has a d...

Significance The retina is considered a window to the brain, and retinal degenerative diseases involve the same mechanisms as those of other neurodegenerative disorders. Neuronal degeneration is a complex process involving environmental stress, which can affect vulnerable neurons. High-fat diet–induced metabolic alterations may influence retinal ho...

Fatty acids, and especially docosahexaenoic acid (DHA), are essential for photoreceptor cell integrity and are involved in the phototransduction cascade. In this study, we analyzed the changes in the fatty acid profile in the retina of the rd10 mouse model of retinitis pigmentosa in order to identify potential risk factors for retinal degeneration...

The gut microbiome is known to influence the pathogenesis and progression of neurodegenerative diseases. However, there has been relatively little focus upon the implications of the gut microbiome in retinal diseases such as retinitis pigmentosa (RP). Here, we investigated changes in gut microbiome composition linked to RP, by assessing both retina...

Objective Considering the demonstrated implication of the retina in Parkinson disease (PD) pathology and the importance of dopaminergic cells in this tissue, we aimed to analyze the state of the dopaminergic amacrine cells and some of their main postsynaptic neurons in the retina of PD. Methods Using immunohistochemistry and confocal microscopy, w...

Purpose: Retinitis pigmentosa (RP) is a blinding neurodegenerative disease of the retina that can be affected by many factors. The present study aimed to analyze the effect of different environmental light intensities in rd10 mice retina. Methods: C57BL/6J and rd10 mice were bred and housed under three different environmental light intensities:...

Background/aims: It is well established that oxidative stress and inflammation are common pathogenic features of retinal degenerative diseases. ITH12674 is a novel compound that induces the transcription factor Nrf2; in so doing, the molecule exhibits anti-inflammatory, and antioxidant properties, and affords neuroprotection in rat cortical neuron...

Optical coherence tomography (OCT) and OCT angiography (OCTA) have been a technological breakthrough in the diagnosis, treatment, and follow-up of many retinal diseases, thanks to its resolution and its ability to inform of the retinal state in seconds, which gives relevant information about retinal degeneration. In this review, we present an immun...

Melanopsin-containing retinal ganglion cells (mRGCs) represent a third class of retinal photoreceptors involved in regulating the pupillary light reflex and circadian photoentrainment, among other things. The functional integrity of the circadian system and melanopsin cells is an essential component of well-being and health, being both impaired in...

The innate immune Toll-like receptor (TLR) family plays essential roles in cell proliferation, survival and function of the central nervous system. However, the way in which TLRs contribute to the development and maintenance of proper retinal structure and function remains uncertain. In this work, we assess the effect of genetic TLR4 deletion on th...

In retinal degenerative diseases, the progressive death of neuronal cells is accompanied by retinal remodeling, together with alterations of retinal vascularization and functional deterioration, with a decrease in the electric response and visual acuity. Oxidative stress, apoptosis and inflammation are crucial pathways underlying the gradual photor...

Ocular pathologies and blindness have been linked to circadian disorders. In previous studies, our group has demonstrated that retinitis pigmentosa is associated with degenerative changes in the melanopsin system and weaker circadian patterns. We have also shown that cannabinoids preserve retinal structure and function in dystrophic P23H rats. This...

Parkinson's disease (PD) patients often suffer from non-motor symptoms like sleep dysregulation, mood disturbances or circadian rhythms dysfunction. The melanopsin-containing retinal ganglion cells are involved in the control and regulation of these processes and may be affected in PD, as other retinal and visual implications have been described in...

Retinitis pigmentosa (RP) is a group of inherited retinal degenerative diseases involving a progressive degeneration of photoreceptor cells. Following the loss of photoreceptors, retinal vascularization tends to decrease, which seems to play a role in the degenerative process of retinal cells. This study reports changes in retinal vascular network...

Retinal neurodegenerative diseases involve a scenario of inflammation and cell death that leads to morphological alterations and visual impairment. Non-ocular inflammatory processes could affect neurodegenerative retinal disorders and their progression, at least in part by activating microglial cells and releasing pro-inflammatory cytokines. Our pu...

Successful drug therapies for treating ocular diseases require effective concentrations of neuroprotective compounds maintained over time at the site of action. The purpose of this work was to assess the efficacy of intravitreal controlled delivery of tauroursodeoxycholic acid (TUDCA) encapsulated in poly(D,L-lactic-co-glycolic acid) (PLGA) microsp...

In mammals, melanopsin-expressing retinal ganglion cells (mRGCs) are, among other things, involved in several non-image-forming visual functions, including light entrainment of circadian rhythms. Considering the profound impact of aging on visual function and ophthalmic diseases, here we evaluate changes in mRGCs throughout the life span in humans....

Retinitis pigmentosa (RP) is a degenerative disease leading to photoreceptor cell loss. Mouse models of RP, such as the rd10 mouse (B6.CXBl-Pde6brd10/J), have enhanced our understanding of the disease, allowing for development of potential therapeutics. In 2011, our group first demonstrated that the synthetic progesterone analogue ‘Norgestrel’ is n...

Microglia act as the resident immune cells of the central nervous system, including the retina. In response to damaging stimuli microglia adopt an activated state, which can progress into a phagocytic phenotype and play a potentially harmful role by eliciting the expression and release of pro-inflammatory cytokines. The aim of the present study was...

The melanopsin system consists of intrinsically photosensitive retinal ganglion cells containing the photopigment melanopsin (mRGCs). These mRGCs mediate several non-image-forming visual functions, including light entrainment of circadian rhythms. Here we evaluate age-related alterations of the melanopsin system and circadian rhythms in P23H line 1...

Purpose: Retinitis pigmentosa includes a group of progressive retinal degenerative diseases that affect the structure and function of photoreceptors. Secondarily to the loss of photoreceptors, there is a reduction in retinal vascularization, which seems to influence the cellular degenerative process. Retinal macroglial cells, astrocytes, and Mülle...

Purpose: To characterize the relationship between fundus autofluorescence (FAF), Optical Coherence Tomography (OCT) and immunohistochemistry over the course of chronic retinal degeneration in the P23H rat. Methods: Homozygous albino P23H rats, Sprague-Dawley (SD) rats and pigmented Long Evans (LE) rats were used. A Spectralis HRA OCT system was...

Retinal ganglion cell degeneration underlies the pathophysiology of diseases affecting the retina and optic nerve. Several studies have previously evidenced the anti-apoptotic properties of the bile constituent, tauroursodeoxycholic acid, in diverse models of photoreceptor degeneration. The aim of this study was to investigate the effects of system...

All retinal disorders, regardless of their aetiology, involve the activation of oxidative stress and apoptosis pathways. The administration of neuroprotective factors is crucial in all phases of the pathology, even when vision has been completely lost. The retina is one of the most susceptible tissues to reactive oxygen species damage. On the other...

Background Retinitis pigmentosa is a heterogeneous group of inherited neurodegenerative retinal disorders characterized by a progressive peripheral vision loss and night vision difficulties, subsequently leading to central vision impairment. Chronic microglia activation is associated with various neurodegenerative diseases including retinitis pigme...

Cannabinoids have been demonstrated to exert neuroprotective effects on different types of neuronal insults. Here we have addressed the therapeutic potential of the synthetic cannabinoid HU210 on photoreceptor degeneration, synaptic connectivity and functional activity of the retina in the transgenic P23H rat, an animal model for autosomal dominant...

Purpose: To evaluate quantitative and qualitative age-related changes in intrinsically photosensitive melanopsin-containing retinal ganglion cells (ipRGCs) in transgenic P23H rats, an animal model of autosomal dominant retinitis pigmentosa (RP) was examined. Methods: ipRGC density, morphology, and integrity were characterized by immunohistochemi...

Proinsulin has been characterized as a neuroprotective molecule. In this work we assess the therapeutic potential of proinsulin on photoreceptor degeneration, synaptic connectivity and functional activity of the retina in the transgenic P23H rat, an animal model of autosomal dominant retinitis pigmentosa (RP). P23H homozygous rats received an intra...

Saffron, an extract from Crocus sativus, has been largely used in traditional medicine for its antiapoptotic and anticarcinogenic properties. In this work, we investigate the effects of safranal, a component of saffron stigmas, in attenuating retinal degeneration in the P23H rat model of autosomal dominant retinitis pigmentosa. We demonstrate that...

Parkinson's disease (PD) is a neurodegenerative disorder that also involves circadian rhythm alterations. Modifications of circadian rhythm parameters have been shown to occur in both PD patients and toxin-induced PD animal models. In the latter case, rotenone, a potent inhibitor of mitochondrial complex I (nicotinamide adenine dinucleotide [NADH]-...

To evaluate the preventive effect of tauroursodeoxycholic acid (TUDCA) on photoreceptor degeneration, synaptic connectivity and functional activity of the retina in the transgenic P23H rat, an animal model of autosomal dominant retinitis pigmentosa (RP). P23H line-3 rats were injected with TUDCA once a week from postnatal day (P)21 to P120, in para...

This study focuses on the effects of retinal degeneration on the circadian patterns of P23H rats, as well as on the effect of exogenous melatonin administration. To this end, the body temperature of P23H and Sprague-Dawley rats was continuously monitored and their retinas examined at different stages of degeneration, by means of histological labeli...

Some evidence suggests that retinal pigment epithelium (RPE) can express nicotinic acetylcholine receptors (nAChRs) as described for other epithelial cells, where nAChRs have been involved in processes such as cell development, cell death, cell migration, and angiogenesis. This study is designed to determine the expression and activity of α7 nAChRs...

The effect of constant darkness (DD) and constant light (LL) on the circadian pattern of macronutrient self-selection, daily food intake and body weight was analysed in rats using an automated computer system. No significant differences in energy intake were observed between groups as regards energy intake or macronutrient preferences. Fat and CHO...

There is limited data regarding the effects of melatonin on the activity of neuronal acetylcholine receptors (nAChRs) themselves. This study analyzes the effects of low concentrations of melatonin on nicotine-evoked currents from cerebellar granule neurons (CGNs) in culture. Using electrophysiological and Ca(2+)-imaging techniques, it was found a s...

We have studied the effects of BW284c51 on the function of Torpedo nicotinic acetylcholine (Ach) receptors (nAchRs) transplanted to Xenopus laevis oocytes. BW284c51 reversible inhibited Ach-elicited currents (IAch) in a concentration-dependent manner, increased IAch desensitisation and changed the Ach concentration-dependence of the IAch from a two...

The neuronal alpha7 nicotinic acetylcholine (ACh) receptor is believed to be a highly Ca(2+) permeable ligand-gated receptor-channel. However, the contribution of Ca(2+) to cationic current generated by ACh has not yet been directly measured to date. Simultaneous fluorescence and whole-cell current measurements using the Ca(2+) indicator dye fura-2...

The materno-fetal transfer of metabolites and nutrients requires the operation of specific transport mechanisms through syncytiotrophoblast membranes. Electrophysiological studies on these cells are scarce and, because of their syncytial nature, whole-cell current recordings have not been carried out. We have now studied whether or not ion channels...

Experiments were conducted in both HEK cells and cerebellar neurons to investigate whether CXC chemokine receptor 2 (CXCR2) is functionally coupled to GluR1. The co-expression of CXCR2 with GluR1 in HEK cells increased (i) the GluR1 "apparent" affinity for the transmitter; (ii) the GluR1 channel open probability; and (iii) GluR1 binding site cooper...

The Ca(2+) permeability of the human heteromeric alpha 3 beta 4, alpha 4 beta 2 and alpha 4 beta 4 neuronal nicotinic acetylcholine receptors (nAChRs) was estimated by measuring the fractional Ca(2+) current (P(f)) flowing through the ligand-activated receptor-channels. Simultaneous recordings of transmembrane currents and fluorescence transients,...

The nicotine-induced modulation of the synaptic activity was studied in cultured spinal cord neurons from embryonic rats, using the patch-clamp technique, alone or in combination with Ca(2+) imaging. Morphologically, neurons could be divided into two populations: multipolar nerve cells and bipolar, spindle-shaped neurons. Neurons were predominantly...

The effect of 4-h feeding cycles on the feeding pattern of rats kept under constant light and constant darkness, was analysed. In both cases, the scheduled pattern of food-approach behavior elicited dissociation of the feeding activity into several components associated to the feeding times (CAFT), which coexisted with the previous circadian free-r...

The wheel running (WR) and feeding activity (FA) of Octodon degus, a new laboratory rodent characterized by its diurnal habits, were recorded under different lighting conditions. Under 12:12-h light-dark (LD 12:12) cycles, WR activity exhibited a crepuscular pattern with two peaks, M and E, associated with "dawn" and "dusk," respectively. In both c...

It has been suggested that two endogenous timekeeping systems, a light-entrainable pacemaker (LEP) and a food-entrainable pacemaker (FEP), control circadian rhythms. To understand the function and interaction between these two mechanisms better, we studied two behavioral circadian rhythmicities, feeding and locomotor activity, in rats exposed to tw...

The daily caloric intake and circadian pattern of macronutrient self-selection were examined in rats subjected to 3 h of food and water deprivation at the beginning or at the end of darkness. When one sole 3-h period of deprivation was applied, rats showed a compensatory response characterized by an unscheduled diurnal and nocturnal increase in the...

The entrainment limits of the circadian rhythms of feeding activity were studied in Wistar rats exposed to gradually increasing and decreasing or to static light-dark cycles. In the former, the entrainment limits of feeding behavior were 22 h 10 min and 26 h 40 min. In the latter, the upper limit was higher, because rats under zeitgeber period (t)...

Exercise is recognized to affect circadian rhythmicity in a variety of ways. It masks the expression of other behavioral and physiological rhythms, entrains the master pacemaker, and influences the free-running period of other rhythms. In this paper we study the influence of exercise on the organization of the timing system by analyzing the effect...

We describe and test a programmable feeding system based on a contact eatometer, previously developed in our laboratory, consisting of a swinging grid beneath a hopper that is moved by the rat each time it wants to eat. This has not been connected to a solenoid that can block the movement of the grid to prevent access to the food. It also provides...