Retinal and lenticular ultrastructure in the aestivating salamanderfish, Lepidogalaxias salamandroides (Galaxiidae, Teleostei) with special reference to a new type of photoreceptor mosaic

The salamanderfish, Lepidogalaxias salamandroides (Galaxiidae, Teleostei) is endemic to southwestern Australia and inhabits shallow, freshwater pools which evaporate during the hot summer months. Burrowing into the substrate in response to falling water levels allows these fish to aestivate for extended periods of time while encapsulated in a mucous cocoon even when the pools contain no water. Only a few minutes after a major rainfall, these fish emerge into relatively clear water which subsequently becomes laden with tannin, turning the water black and reducing the pH to approximately 4.3. As part of a large study of the visual adaptations of this unique species, the retinal and lenticular morphology of the aestivating salamanderfish is examined at the level of the light and electron microscopes. The inner retina is highly vascularised by a complex system of vitreal blood vessels, while the outer retina receives a blood supply by diffusion from a choriocapillaris. This increased retinal blood supply may be an adaptation for reducing the oxygen tension during critical periods of aestivation. Large numbers of Muller cells traverse the thickness of the retina from the inner to the outer limiting membranes. The ganglion cells are arranged in two ill-defined layers, separated from a thick inner nuclear layer containing two layers of horizontal cells by a soma-free inner plexiform layer. The photoreceptors can be divided into three types typical of many early actinopterygian representatives; equal double cones, small single cones and large rods (2:1:1). These photoreceptors are arranged into a unique regular square mosaic comprising a large rod bordered by four equal double cones with a small single cone located at the corner of each repeating unit. The double cones may optimise perception of mobile prey which it tracks by flexion of its head and neck and the large rods may increase sensitivity in the dark tannin-rich waters in which it lives. Each single cone also possesses a dense collection of polysomes and glycogen (a paraboloid) beneath its ellipsoid, the first such finding in teleosts. The retinal pigment epithelium possesses melanosomes, pha,oocytes and a large number of mitochondria. The anatomy of the retina and the photoreceptor mosaic is discussed in relation to the primitive phylogeny of this species and its unique life history.

Phagocytosis of Photoreceptor Outer Segments by Transplanted Human Neural Stem Cells as a Neuroprotective Mechanism in Retinal Degeneration

Purpose. Transplantation of human central nervous system stem cells (HuCNS-SC) into the subretinal space of Royal College of Surgeons (RCS) rats preserves photoreceptors and visual function. To explore possible mechanism(s) of action underlying this neuroprotective effect, we performed a detailed morphologic and ultrastructure analysis of HuCNS-SC transplanted retinas. Methods. The HuCNS-SC were transplanted into the subretinal space of RCS rats. Histologic examination of the transplanted retinas was performed by light and electron microscopy. Areas of the retina adjacent to HuCNS-SC graft (treated regions) were analyzed and compared to control sections obtained from the same retina, but distant from the transplant site (untreated regions). Results. The HuCNS-SC were detected as a layer of STEM 121 immunopositive cells in the subretinal space. In treated regions, preserved photoreceptor nuclei, as well as inner and outer segments were identified readily. In contrast, classic signs of degeneration were observed in the untreated regions. Interestingly, detailed ultrastructure analysis revealed a striking preservation of the photoreceptor–bipolar–horizontal cell synaptic contacts in the outer plexiform layer (OPL) of treated areas, in stark contrast with untreated areas. Finally, the presence of phagosomes and vesicles exhibiting the lamellar structure of outer segments also was detected within the cytosol of HuCNS-SC, indicating that these cells have phagocytic capacity in vivo. Conclusions. This study reveals the novel finding that preservation of specialized synaptic contacts between photoreceptors and second order neurons, as well as phagocytosis of photoreceptor outer segments, are potential mechanism(s) of HuCNS-SC transplantation, mediating functional rescue in retinal degeneration.

The foveal photoreceptor mosaic in the pipefish, Corythoichthyes paxtoni (Syngnathidae, Teleostei)

The foveal and non-foveal retinal regions of the pipefish, Corythoichthyes paxtoni (Syngnathidae, Teleostei) are examined at the level of the light and electron microscopes. The pipefish possesses a deep, pit (convexiclivate) fovea which, although lacking the displacement of the inner retinal layers as described in other vertebrate foveae, is characterised by the exclusion of rods, a marked increase in the density of photoreceptors and a regular square mosaic of four double cones surrounding a central single cone. In the perifoveal and peripheral retinal regions, the photoreceptor mosaic is disrupted by the insertion of large numbers of rods, which reduce spatial resolving power but may uniformly increase sensitivity for off-axis rays. In addition to a temporal fovea subtending the frontal binocular field, there is also a central area centralis subtending the monocular visual field. Based on morphological comparisons with other foveate teleosts, four foveal types are characterised and foveal function discussed with respect to the theoretical advantage of a regular square mosaic.

Cell Adhesion Peptide RGDSP and Laminin Support Proliferation and Migration of Postnatal Retinal Stem Cells in a 3D Hydrogel Culture System

Purpose: Retinal stem cells (RSCs) can be isolated from radial glia population of the newborn mouse retina (Angénieux et al., 2006). These RSCs have great capacity to renew and generate neurons including cells differentiated towards the photoreceptor lineage (Mehri-Soussi et al., 2006). However, our published results showed poor integration and survival rate after cell grafting into the retina. The uncontrollable environment of retina seems to be the problem. To bypass this, we are trying to generate hemi-retinal tissue in vitro that can be used for transplantation. Methods: Expanded RSCs were seeded in a mixture of poly-ethylene-glycol (PEG)-polymer-based hydrogels crosslinked by peptides that also serve as substrates for matrix metalloproteinases. Different doses of crosslinker peptides were tested. Several growth factors were studied to stimulate cell proliferation and differentiation. Results: Cells were trapped in hydrogels and cultured in the presence of FGF2 and EGF. Spherical cell clusters indicating proliferation appeared within several days, but there was no cell migration within the gel. We then added cell adhesion molecules integrin ligand RGDSP, or laminin, or a combination of both, into the gel. Cells grown with laminin showed the best proliferation. Cells grown with RGDSP proliferated a few times and then started to spread out. Cells grown with the combination of RGDSP and laminin showed better proliferation than with RGDSP alone and larger spread-outs than with laminin alone. After stimulations with first FGF2 and EGF, and then only FGF2, some cells showed neuronal morphology after 2 weeks. The neuronal population was assessed by the presence of neuronal marker b-tubulin-III. Glial cells were also present. Further characterizations are undergoing. Conclusions: RSC can grow and migrate in 3D hydrogel with the addition of FGF2, EGF, RGDSP and laminin. Further developments are necessary to form a homogenous tissue containing retinal cells.

Dual role of Bmi1 loss in the preservation of photoreceptor layers in the Rd1 mouse

Purpose: In the Rd1 and Rd10 mouse models of retinitis pigmentosa, a mutation in the Pde6ß gene leads to the rapid loss of photoreceptors. As in several neurodegenerative diseases, Rd1 and Rd10 photoreceptors re-express cell cycle proteins prior to death. Bmi1 regulates cell cycle progression through inhibition of CDK inhibitors, and its deletion efficiently rescues the Rd1 retinal degeneration. The present study evaluates the effects of Bmi1 loss in photoreceptors and Müller glia, since in lower vertebrates, these cells respond to retinal injury through dedifferentiation and regeneration of retinal cells. Methods: Cell death and Müller cell activation were analyzed by immunostaining of wild-type, Rd1 and Rd1;Bmi1-/- eye sections during retinal degeneration, between P10 and P20. Lineage tracing experiments use the GFAP-Cre mouse (JAX) to target Müller cells. Results: In Rd1 retinal explants, inhibition of CDKs reduces the amount of dying cells. In vivo, Bmi1 deletion reduces CDK4 expression and cell death in the P15 Rd1;Bmi1-/- retina, although cGMP accumulation and TUNEL staining are detected at the onset of retinal degeneration (P12). This suggests that another process acts in parallel to overcome the initial loss of Rd1;Bmi1-/- photoreceptors. We demonstrate here that Bmi1 loss in the Rd1 retina enhances the activation of Müller glia by downregulation of p27Kip1, that these cells migrate toward the ONL, and that some cells express the retinal progenitor marker Pax6 at the inner part of the ONL. These events are also observed, but to a lesser extent, in Rd1 and Rd10 retinas. At P12, EdU incorporation shows proliferating cells with atypical elongated nuclei at the inner border of the Rd1;Bmi1-/- ONL. Lineage tracing targeting Müller cells is in process and will determine the implication of this cell population in the maintenance of the Rd1;Bmi1-/- ONL thickness and whether downregulation of Bmi1 in Rd10 Müller cells equally stimulates their activation. Conclusions: Our results show a dual role of Bmi1 deletion in the rescue of photoreceptors in the Rd1;Bmi1-/- retina. Indeed, the loss of Bmi1 reduces Rd1 retinal degeneration, and as well, enhances the Müller glia activation. In addition, the emergence of cells expressing a retinal progenitor marker in the ONL suggests Bmi1 as a blockade to the regeneration of retinal cells in mammals.

Role of the chemokine receptor CX3CR1 in the mobilization of phagocytic retinal microglial cells.

We recently showed that subretinal CX3CR1-dependent microglial cell (MC) accumulation may lead to age-related macular degeneration. The fate of MC after engulfing retinal debris is poorly understood. Severe photoreceptor degeneration was observed 40days after exposure to bright light in CX3CR1-deficient but not control mice, and more MCs accumulated in the subretinal space of the former than the latter. To study the fate of subretinal MCs in CX3CR1 competent animals, we used a dystrophic rat model in which abundant subretinal MC accumulation is observed secondary to retinal degeneration. In dystrophic rats, MCs containing rhodopsin or rod outer segment (ROS) debris were found outside the outer retina at sites suggesting choroidal and ciliary egress. In conclusion, our data indicate that MC accumulation at injury sites is independent of CX3CR1 and precedes photoreceptor degeneration. The ectopic presence of rhodopsin-positive MCs suggests that CX3CR1 participates in MC egress from the outer retina.

Retinal degeneration progression changes lentiviral vector cell targeting in the retina.

In normal mice, the lentiviral vector (LV) is very efficient to target the RPE cells, but transduces retinal neurons well only during development. In the present study, the tropism of LV has been investigated in the degenerating retina of mice, knowing that the retina structure changes during degeneration. We postulated that the viral transduction would be increased by the alteration of the outer limiting membrane (OLM). Two different LV pseudotypes were tested using the VSVG and the Mokola envelopes, as well as two animal models of retinal degeneration: light-damaged Balb-C and Rhodopsin knockout (Rho-/-) mice. After light damage, the OLM is altered and no significant increase of the number of transduced photoreceptors can be obtained with a LV-VSVG-Rhop-GFP vector. In the Rho-/- mice, an alteration of the OLM was also observed, but the possibility of transducing photoreceptors was decreased, probably by ongoing gliosis. The use of a ubiquitous promoter allows better photoreceptor transduction, suggesting that photoreceptor-specific promoter activity changes during late stages of photoreceptor degeneration. However, the number of targeted photoreceptors remains low. In contrast, LV pseudotyped with the Mokola envelope allows a wide dispersion of the vector into the retina (corresponding to the injection bleb) with preferential targeting of Müller cells, a situation which does not occur in the wild-type retina. Mokola-pseudotyped lentiviral vectors may serve to engineer these glial cells to deliver secreted therapeutic factors to a diseased area of the retina.

Retinal degeneration progression changes lentiviral vector cell targeting in the retina

Ce travail de thèse a été réalisé au sein de l'Unité de Thérapie Génique et Biologie des Cellules Souches de l'Hôpital Jules- Gonin dans le Service d'Ophtalmologie de l'Université de Lausanne. Ce laboratoire recherche des solutions thérapeutiques pour des maladies dégénératives et incurables de la rétine comme les rétinites pigmentaires (RP). Ayant déjà montré certains résultats dans le domaine, la thérapie génique a été notre outil pour ce travail. Cette méthode se base sur le principe de remplacer un gène déficient par sa copie normale, en transportant celle-ci au coeur même du noyau par un vecteur. Il existe à l'heure actuelle différents vecteurs. Un des plus efficaces est un vecteur viral non-réplicatif : le lentivirus, dérivé de HIV-1. Celui-ci a la capacité d'intégrer le génome de la cellule cible, lui conférant ainsi un nouveau matériel génétique. Notre but a été d'établir le tropisme du lentivirus dans une rétine en dégénérescence. Ce lentivirus est connu pour transduire efficacement les cellules de l'épithélium pigmentaire rétinien dans l'oeil adulte sain, ainsi que celles de la neurorétine, mais ce, uniquement durant le développement. On sait aussi que le vecteur lentiviral présente un tropisme différent selon les enveloppes dont il est muni ; par exemple, le lentivirus avec une enveloppe Mokola est connu pour transduire les cellules gliales du système nerveux central. La rétine qui dégénère montre quant à elle des changements de sa structure qui pourraient influencer la diffusion du vecteur et/ou son tropisme. Le postulat de base a été le suivant : chez l'adulte, la transduction des neurones de la rétine via le lentivirus pourrait être facilitée par l'altération de la membrane limitante externe induite par la dégénérescence (meilleure pénétrance du virus). D'un point de vue technique, nous avons utilisé deux types distincts de modèles murins de dégénérescence rétinienne : des souris Balb/C soumises à une dose toxique de lumière et les souris Rhodopsin knockout, animaux génétiquement modifiés. Comme vecteur viral, nous avons employé deux différents pseudotypes de lentivirus (caractérisés par les enveloppes virales) avec différents promoteurs (séquence d'ADN qui initie la transduction et confère la spécificité d'expression d'un gène). En changeant l'enveloppe et le promoteur, nous avons essayé de trouver la meilleure combinaison pour augmenter l'affinité du vecteur vis-à-vis des photorécepteurs d'abord, puis vis-à-vis d'autres cellules de la rétine. Nos résultats ont montré que la membrane limitante externe est effectivement altérée chez les deux modèles de dégénérescence, mais que cette modification ne favorise pas la transduction des photorécepteurs lorsqu'on utilise un vecteur lentiviral contenant une enveloppe VSVG et un promoteur photorécepteur-spécifique ou ubiquitaire. En effet, une forte réaction gliale a été observée. Par contre, en utilisant le lentivirus avec une enveloppe Mokola et un promoteur ubiquitaire, nous avons constaté une très bonne transduction au niveau des cellules de Millier dans la rétine en dégénérescence, phénomène non observé chez les souris sauvages. Ce travail a donc permis de trouver un vecteur viral efficace pour atteindre et transduire les cellules de Miiller, ceci seulement pendant la dégénérescence de la rétine. Ces cellules, une fois transduites, pourraient être utilisées pour sécréter dans la rétine des agents thérapeutiques tels que des facteurs neurotrophiques pour soutenir la survie des photorécepteurs ou des facteurs anti-angiogéniques pour prévenir la néo-vascularisation lors de diabète ou de dégénérescence maculaire liée à l'âge. - In normal mice, the lentiviral vector (LV) is very efficient to target the RPE cells, but transduces retinal neurons well only during development. In the present study, the tropism of LV has been investigated in the degenerating retina of mice, knowing that the retina structure changes during degeneration. We postulated that the viral transduction would be increased by the alteration of the iuter limiting membrane (OLM). Two different LV pseudotypes were tested using the VSVG arid the Mokola envelopes, as well as two animal models of retinal degeneration: light-damaged Balb-C and Rhodopsin knockout (Rho-/-) mice. After light damage, the OLM is altered and no significant increase of the number of transduced photoreceptors can be obtained with a LV-VSVG-Rhop-GFP vector. In the Rho-/- mice, an altération of the OLM was also observed, but the possibility of transducing photoreceptors was decreased, probably by ongoing gliosis. The use of a ubiquitous promoter allows better photoreceptor transduction, suggesting that photoreceptór-specific promoter activity change during late stages of photoreceptor degeneration. However, the number of targeted photoreceptors remains low. In contrast, LV pseudotyped with the tfokola envelope allows a wide dispersion of the ctor into the retina (corresponding to the injection bleb) with preferential targeting of Muller cells, a situation Mc\ does ot occur in the wild- type retina. Mokola-pseudotyped lentiviral vectors may serve to engineer these glial cells to deliver secreted therapeutic factors to a diseased area of the retina.

Retinal degeneration depends on Bmi1 function and reactivation of cell cycle proteins.

The epigenetic regulator Bmi1 controls proliferation in many organs. Reexpression of cell cycle proteins such as cyclin-dependent kinases (CDKs) is a hallmark of neuronal apoptosis in neurodegenerative diseases. Here we address the potential role of Bmi1 as a key regulator of cell cycle proteins during neuronal apoptosis. We show that several cell cycle proteins are expressed in different models of retinal degeneration and required in the Rd1 photoreceptor death process. Deleting E2f1, a downstream target of CDKs, provided temporary protection in Rd1 mice. Most importantly, genetic ablation of Bmi1 provided extensive photoreceptor survival and improvement of retinal function in Rd1 mice, mediated by a decrease in cell cycle markers and regulators independent of p16(Ink4a) and p19(Arf). These data reveal that Bmi1 controls the cell cycle-related death process, highlighting this pathway as a promising therapeutic target for neuroprotection in retinal dystrophies.

Deleterious Actions Of Vegf On The Blood Retinal Barrier And Photoreceptor Survival In The Light-damage Model

Purpose: The retinal balance between pro- and anti-angiogenic factors is critical for angiogenesis control, but is also involved in cell survival. We previously reported upregulation of VEGF and photoreceptor (PR) cell death in the Light-damage (LD) model. Preliminary results showed that anti-VEGF can rescue PR from cell death. Thus, we investigated the role of VEGF on the retina and we herein described the effect of anti-VEGF antibody delivered by lentiviral gene transfer in this model.Methods: To characterize the action of VEGF during the LD, we exposed Balb/c mice subretinally injected with LV-anti-VEGF, or not, to 5'000 lux for 1h. We next evaluated the retinal function, PR survival and protein expression (VEGF, VEGFR1/2, Src, PEDF, p38MAPK, Akt, Peripherin, SWL-opsin) after LD. We analyzed Blood retinal barrier (BRB) integrity on flat-mounted RPE and cryosections stained with β-catenin, ZO-1, N-cadherin and albumin.Results: Results indicate that the VEGF pathway is modulated after LD. LD leads to extravascular albumin leakage and BRB breakdown: β-catenin, ZO-1 and N-cadherin translocate to the cytoplasm of RPE cells showing loss of cell cohesion. This phenomenon is in adequacy with the VEGF time-course expression. Assessment of the retinal function reveals that PR rescue correlates with the level of LV-anti-VEGF expression. Rhodopsin content was higher in the LV-anti-VEGF group than in controls and measures of the ONL thickness indicate that LV-anti-VEGF preserves by 82% the outer nuclear layer from degeneration. Outer segments (OS) appeared well organized with an appropriate length in the LV-anti-VEGF group compared to controls, and the expression of SWL-opsin is maintained in the OS without being mislocalized as in the LV-GFP group. Finally, LV-anti-VEGF treatment prevents BRB breakdown and maintained RPE cell integrity.Conclusions: This study involves VEGF in LD and highlights the prime importance of the BRB integrity for PR survival. Taken together, these results show that anti-VEGF is neuroprotective in this model and maintains functional PR layer in LD-treated mice.

In conditions of limited chromophore supply rods entrap 11-cis-retinal leading to loss of cone function and cell death.

RPE65 is a retinoid isomerase required for the production of 11-cis-retinal, the chromophore of both cone and rod visual pigments. We recently established an R91W knock-in mouse strain as homologous animal model for patients afflicted by this mutation in RPE65. These mice have impaired vision and can only synthesize minute amounts of 11-cis-retinal. Here, we investigated the consequences of this chromophore insufficiency on cone function and pathophysiology. We found that the R91W mutation caused cone opsin mislocalization and progressive geographic cone atrophy. Remnant visual function was mostly mediated by rods. Ablation of rod opsin corrected the localization of cone opsin and improved cone retinal function. Thus, our analyses indicate that under conditions of limited chromophore supply rods and cones compete for 11-cis-retinal that derives from regeneration pathway(s) which are reliant on RPE65. Due to their higher number and the instability of cone opsin, rods are privileged under this condition while cones suffer chromophore deficiency and degenerate. These findings reinforce the notion that in patients any effective gene therapy with RPE65 needs to target the cone-rich macula directly to locally restore the cones' chromophore supply outside the reach of rods.

Cell Cycle Proteins and Retinal Degeneration: Evidences of New Potential Therapeutic Targets.

During different forms of neurodegenerative diseases, including the retinal degeneration, several cell cycle proteins are expressed in the dying neurons from Drosophila to human revealing that these proteins are a hallmark of neuronal degeneration. This is true for animal models of Alzheimer's, and Parkinson's diseases, Amyotrophic Lateral Sclerosis and for Retinitis Pigmentosa as well as for acute injuries such as stroke and light damage. Longitudinal investigation and loss-of-function studies attest that cell cycle proteins participate to the process of cell death although with different impacts, depending on the disease. In the retina, inhibition of cell cycle protein action can result to massive protection. Nonetheless, the dissection of the molecular mechanisms of neuronal cell death is necessary to develop adapted therapeutic tools to efficiently protect photoreceptors as well as other neuron types.

A direct contact between astrocyte and vitreous body is possible in the rabbit eye due to discontinuities in the basement membrane of the retinal inner limiting membrane

Different from most mammalian species, the optic nerve of the rabbit eye is initially formed inside the retina where myelination of the axons of the ganglion cells starts and vascularization occurs. Astrocytes are confined to these regions. The aforementioned nerve fibers known as medullated nerve fibers form two bundles that may be identified with the naked eye. The blood vessels run on the inner surface of these nerve fiber bundles (epivascularization) and, accordingly, the accompanying astrocytes lie mostly facing the vitreous body from which they are separated only by the inner limiting membrane of the retina. The arrangement of the astrocytes around blood vessels leads to the formation of structures known as glial tufts. Fragments (N = 3) or whole pieces (N = 3) of the medullated nerve fiber region of three-month-old male rabbits (Orictolagus cuniculus) were fixed in glutaraldehyde followed by osmium tetroxide, and their thin sections were examined with a transmission electron microscope. Randomly located discontinuities (up to a few micrometers long) of the basement membrane of the inner limiting membrane of the retina were observed in the glial tufts. As a consequence, a direct contact between the astrocyte plasma membrane and vitreous elements was demonstrated, making possible functional interactions such as macromolecular exchanges between this glial cell type and the components of the vitreous body.

Development and disease of the photoreceptor cilium

Primary cilia are microtubule-rich hair-like extensions protruding from the surface of most post-mitotic cells. They act as sensory organelles that help interpret various environmental cues. Mutations in genes encoding proteins involved in ciliogenesis or protein transport to the primary cilia lead to a wide variety of diseases commonly referred to as ciliopathies,which include primary ciliary dyskinesia, situs invertus, hydrocephalus, kidney diseases, respiratory diseases, and retinal degenerations. In the retina, the photoreceptor cells have a highly specialized primary cilium called the outer segment (OS), which is essential for photosensation. Development of the photoreceptor OS shares key regulatory mechanisms with ciliogenesis in other cell types. Accumulating evidence indicates that mutations that affect OS development and/or protein transport to the OS generally lead to photoreceptor degeneration, which can be accompanied by a range of other clinical manifestations due to the dysfunction of primary cilia in different cell types. Here, we review the general mechanisms regulating ciliogenesis, and present different examples of mutations affecting OS ciliogenesis and protein transport that lead to photoreceptor degeneration. Overall, we conclude that the genetic and molecular evidence accumulated in recent years suggest a clear link between the development and function of the primary cilium and various clinical conditions. Future studies aimed at uncovering the cellular and molecular mechanisms implicated in ciliogenesis in a wide variety of animal models should greatly increase our understanding of the pathophysiology of many human diseases, including retinal degenerations.

Cambios maculares y de capa de fibras nerviosas ganglionares posterior a la vitrectomía pars plana y sus factores pronósticos en la fundación oftalmológica nacional

OBJETIVOS: Determinar los factores pronóstico, cambios maculares morfológicos y de capa de fibras nerviosas ganglionares posterior a vitrectomía pars plana, en la Fundación Oftalmológica Nacional. MATERIALES Y MÉTODOS: Estudio longitudinal de antes y después (3y6 meses) de la vitrectomía pars plana (VPP) en pacientes con membrana epirretiniana, agujero macular, síndrome de tracción vítreo macular y opacidades vítreas no-inflamatorias. Se realizó seguimiento clínico y con tomografía de coherencia óptica. RESULTADOS: Grupo de 60 pacientes (mujeres 65.0%), edad promedio 65.45+9.49años y tiempo de enfermedad promedio 23+29.79meses. Las indicaciones de VPP (n=60ojos) fueron agujero macular (38.3%) y membrana epirretiniana (36.7%). Se encontró diferencia significativa entre grosor del complejo capa de células ganglionares (CCG)+capa plexiforme interna (CPI) inicial y 3 meses (p=0.039), correlación entre grosor del complejo CCG+CPI al tercer y sexto mes (r=0.704,p<0.001) y grosor del complejo CCG+CPI al tercer mes con grosor foveal central (CFT) al tercer y sexto mes (r=–0.594,p<0.001 y r=–0.595,p=0.001). Mayores de 65años tenían menor grosor de CFNG a 6meses (r=-0.528,p=0.007). El grosor de CFNG promedio y la presencia de la zona elipsoide inicial fueron factores pronósticos de buena agudeza visual al tercer mes de VPP (r2=0.414,p=0.018, y r2=0.414,p=0.010). CONCLUSIÓN: El grosor de CFNG y la presencia de la zona elipsoide inicial tienen alta capacidad predictiva de buena agudeza visual al tercer mes de VPP, y, correlación inversa entre grosor del complejo CCG+CPI con CFT al tercer y sexto mes de VPP.