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Visible light refers to the frequencies within the electromagnetic spectrum that humans can see, encompassing radiation with wavelengths falling between 380 nm to 760 nm. The energy of a single photon increases with its frequency. In the retina, photoreceptor cells contain light-sensitive pigments that absorb light and convert it into electrical stimuli through a process known as phototransduction. However, since the absorption spectrum of photoreceptors closely aligns with blue light (ranging from 400 to 500 nm), exposure to high light intensities or continuous illumination can result in oxidative stress within these cells, leading to a loss of their functionality. Apart from photoreceptor cells, the retina also houses photosensitive ganglion cells, known as intrinsically photosensitive retinal ganglion cells (ipRGCs). These cells relay information to the suprachiasmatic nucleus in the brain, playing a crucial role in modulating melatonin secretion, which in turn helps in synchronizing the body's circadian rhythms and responses to seasonal changes. Both, ipRGCs and skin possess a peak sensitivity to blue wavelengths, rendering them particularly susceptible to the effects of excessive blue light exposure. This study delves into the consequences of excessive illumination and/or prolonged exposure to blue light on retinal function and explores its implications for human health.

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La tomografía de coherencia óptica se ha convertido en el sistema de imagen más común para detectar de manera precoz el daño glaucomatoso; de ahí que resulte imprescindible para las decisiones clínicas y como criterio de inclusión en investigaciones y ensayos clínicos. El objetivo es exponer los avances en la aplicación de la tomografía de coherencia óptica en la detección del glaucoma a través de la revisión de las publicaciones de los últimos cinco años. La búsqueda se realizó en Google Académico para lo cual se emplearon palabras clave. Las mejoras en la tecnología de dominio espectral y de fuente de barrido han permitido la segmentación de células ganglionares, el reconocimiento de la apertura de la membrana de Bruch como punto de referencia para el análisis de los parámetros del disco óptico y el desarrollo de la angiografía sin contraste. Para el diagnóstico de glaucoma se analizó la estructura en tres localizaciones (células ganglionares maculares, capa de fibras neuroretiniana peripapilar, anillo neuroretiniano y copa en el disco óptico) y el plexo vascular superficial en dos (parafoveal y peripapilar). Se recomienda chequear calidad y presencia de artefactos previo al análisis de los resultados; así como complementar estos resultados con el interrogatorio y hallazgos al examen oftalmológico, fundamentalmente mediante biomicroscopia de polo posterior, para minimizar posibilidad de errores diagnósticos. Es útil tener esto en cuenta, a pesar de que sea numerosa la cantidad de pacientes que acuden cada día a la clínica del glaucoma. Se señalan ventajas y limitaciones de los parámetros estructurales y vasculares en el diagnóstico de glaucoma(AU)

Optical coherence tomography has become the most common imaging system for early detection of glaucomatous damage; hence, it is essential for clinical decisions and as a criterion for inclusion in research and clinical trials. The objective is to present the advances in the application of optical coherence tomography in the detection of glaucoma by reviewing the publications of the last five years. The search was performed in Google Scholar using keywords. Improvements in spectral domain and scanning source technology have allowed the segmentation of ganglion cells, the recognition of Bruch's membrane aperture as a reference point for the analysis of optic disc parameters and the development of non-contrast angiography. For the diagnosis of glaucoma, the structure was analyzed in three locations (macular ganglion cells, peripapillary neuroretinal fiber layer, neuroretinal ring and optic disc cup) and the superficial vascular plexus in two (parafoveal and peripapillary). It is recommended to check quality and presence of artifacts prior to the analysis of the results; as well as to complement these results with the interrogation and findings on ophthalmologic examination, mainly by posterior pole biomicroscopy, to minimize the possibility of diagnostic errors. It is useful to keep this in mind, despite the large number of patients that come to the glaucoma clinic every day. Advantages and limitations of structural and vascular parameters in the diagnosis of glaucoma are pointed out(AU)

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BACKGROUND: Hirschsprung's Disease (HD) is characterized by intestinal sub-occlusion and the absence of enteric ganglion cells. A rectal biopsy examination is performed to confirm the diagnosis. In a recent study, we demonstrated that the analysis of 60 sections of rectal mucosa and submucosa stained by H&E may ensure a 90% diagnostic accuracy. Although the need to analyze so many sections makes the process of reading the slides more time-consuming, this encouraged us to study their distribution in the healthy rectal submucosa, to simplify the diagnosis. OBJECTIVES: To develop a method that facilitates HD diagnosis by studying the distribution of ganglion cells in the submucosal plexus. METHODS: Using the calretinin technique, we studied the distribution of plexuses in 60 fragments of rectal submucosa from 19 cadavers. After the study, the reading method created was used for diagnosis in 47 cases of suspected HD, using H&E staining. The accuracy was verified by comparing the results obtained with H&E to those obtained with the acetylcholinesterase technique, the golden standard in our laboratory. RESULTS: The study of submucosal plexus distribution showed that just by examining the submucosal region every 20 µm, approximately, it is possible to locate a ganglionic plexus, and we have already been able to diagnose HD with 93% accuracy. CONCLUSION: The study of ganglion cell distribution enabled the creation of a simplified method for reading the slides. The method applied achieved good accuracy and it can be used as an alternative method in HD diagnosis.

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In vertebrates, arylalkylamine N-acetyltransferase (AANAT; EC 2.3.1.87) is the time-keeping and key regulatory enzyme in melatonin (Mel) biosynthesis. AANAT is present in the pineal gland, retina, and other regions where it is controlled by light, cyclic adenosine monophosphate (cAMP) levels, and the molecular clock. AANAT converts serotonin to N-acetyl serotonin (NAS) and the last enzyme in the pathway, hydroxy-o-methyltransferase (HIOMT), forms Mel by NAS methylation. We have previously shown that AANAT is expressed in chicken retinal ganglion cells (RGCs) during daytime at the level of mRNA and enzyme activity. Here we investigated the presence of AANAT protein and mRNA throughout development in the chicken embryonic retina as well as AANAT expression, phosphorylation, and its sub-cellular localization in primary cultures of retinal neurons from E10 embryonic retinas exposed to blue light (BL) and controls kept in the dark (D). From embryonic days 7-10 (E7-10) AANAT mRNA and protein were visualized mainly concentrated in the forming ganglion cell layer (GCL), while from E17 through postnatal days, expression was detectable all through the different retinal cell layers. At postnatal day 10 (PN10) when animals were subjected to a 12:12 h LD cycle, AANAT was mainly expressed in the GCL and inner nuclear layer cells at noon (Zeitgeber Time (ZT 6)) and in the photoreceptor cell layer at night (ZT 21). Primary cultures of retinal neurons exhibited an induction of AANAT protein when cells were exposed to BL for 1 h as compared with D controls. After BL exposure, AANAT showed a significant change in intracellular localization from the cytoplasm to the nucleus in the BL condition, remaining in the nucleus 1-2 h in the D after BL stimulation. BL induction of nuclear AANAT was substantially inhibited when cultures were treated with the protein synthesis inhibitor cycloheximide (CHD). Furthermore, the phosphorylated form of the enzyme (pAANAT) increased after BL in nuclear fractions obtained from primary cultures as compared with D controls. Finally, the knockdown of AANAT by sh-RNA in primary cultures affected cell viability regardless of the light condition. AANAT knockdown also affected the redox balance, sh-AANAT treated cultures showing higher levels of reactive oxygen species (ROS) than in the sh-control. Our results support the idea that AANAT is a BL-sensing enzyme in the inner retina of diurnal vertebrates, undergoing phosphorylation and nuclear importation in response to BL stimulation. Moreover, it can be inferred that AANAT plays a novel role in nuclear function, cell viability, and, likely, through redox balance regulation.

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Early life stress (ELS) is defined as a period of severe and/or chronic trauma, as well as environmental/social deprivation or neglect in the prenatal/early postnatal stage. Presently, the impact of ELS on the retina in the adult stage is unknown. The long-term consequences of ELS at retinal level were analyzed in an animal model of maternal separation with early weaning (MSEW), which mimics early life maternal neglect. For this purpose, mice were separated from the dams for 2 h at postnatal days (PNDs) 4-6, for 3 h at PNDs 7-9, for 4 h at PNDs 10-12, for 6 h at PNDs 13-16, and weaned at PND17. At the end of each separation period, mothers were subjected to movement restriction for 10 min. Control pups were left undisturbed from PND0, and weaned at PND21. Electroretinograms, visual evoked potentials, vision-guided behavioral tests, retinal anterograde transport, and retinal histopathology were examined at PNDs 60-80. MSEW induced long-lasting functional and histological effects at retinal level, including decreased retinal ganglion cell function and alterations in vision-guided behaviors, likely associated to decreased synaptophysin content, retina-superior colliculus communication deficit, increased microglial phagocytic activity, and retinal ganglion cell loss through a corticoid-dependent mechanism. A treatment with mifepristone, injected every 3 days between PNDs 4 and16, prevented functional and structural alterations induced by MSEW. These results suggest that retinal alterations might be included among the childhood adversity-induced threats to life quality, and that an early intervention with mifepristone avoided ELS-induced retinal disturbances.

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Glaucoma is a multifactorial neurodegenerative disease of the optic nerve currently considered a severe health problem because of its high prevalence, being the primary cause of irreversible blindness worldwide. The most common type corresponds to Primary Open-Angle Glaucoma. Glaucoma produces, among other alterations, a progressive loss of retinal ganglion cells (RGC) and its axons which are the key contributors to generate action potentials that reach the visual cortex to create the visual image. Glaucoma is characterized by Visual Field loss whose main feature is to be painless and therefore makes early detection difficult, causing a late diagnosis and a delayed treatment indication that slows down its progression. Intrinsically photosensitive retinal ganglion cells, which represent a subgroup of RGCs are characterized by their response to short-wave light stimulation close to 480 nm, their non-visual function, and their role in the generation of the pupillary reflex. Currently, the sensitivity of clinical examinations correlates to RGC damage; however, the need for an early damage biomarker is still relevant. It is an urgent task to create new diagnostic approaches to detect an early stage of glaucoma in a prompt, quick, and economical manner. We summarize the pathology of glaucoma and its current clinical detection methods, and we suggest evaluating the pupillary response to chromatic light as a potential biomarker of disease, due to its diagnostic benefit and its cost-effectiveness in clinical practice in order to reduce irreversible damage caused by glaucoma.

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Abstract Background: Hirschsprung's Disease (HD) is characterized by intestinal sub-occlusion and the absence of enteric ganglion cells. A rectal biopsy examination is performed to confirm the diagnosis. In a recent study, we demonstrated that the analysis of 60 sections of rectal mucosa and submucosa stained by H&E may ensure a 90% diagnostic accuracy. Although the need to analyze so many sections makes the process of reading the slides more time-consuming, this encouraged us to study their distribution in the healthy rectal submucosa, to simplify the diagnosis. Objectives: To develop a method that facilitates HD diagnosis by studying the distribution of ganglion cells in the submucosal plexus. Methods: Using the calretinin technique, we studied the distribution of plexuses in 60 fragments of rectal submucosa from 19 cadavers. After the study, the reading method created was used for diagnosis in 47 cases of suspected HD, using H&E staining. The accuracy was verified by comparing the results obtained with H&E to those obtained with the acetylcholinesterase technique, the golden standard in our laboratory. Results: The study of submucosal plexus distribution showed that just by examining the submucosal region every 20 µm, approximately, it is possible to locate a ganglionic plexus, and we have already been able to diagnose HD with 93% accuracy. Conclusion: The study of ganglion cell distribution enabled the creation of a simplified method for reading the slides. The method applied achieved good accuracy and it can be used as an alternative method in HD diagnosis.

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ABSTRACT Purpose: The study aimed to investigate the correlation between arterial hemodynamics measured by color Doppler ultrasonography and retinal microarchitecture parameters determined by spectral-domain optical coherence tomography (SD-OCT) in pseudoexfoliation glaucoma. Methods: This prospective study included 82 participants. Peripapillary retinal nerve fiber layer, ganglion cell inner plexiform layer, and ganglion cell complex values were measured. Ophthalmic artery and central retinal artery flows were evaluated with color Doppler ultrasonography, and resistivity index values were calculated. Results: The study included 47 controls and 35 pseudoexfoliation glaucoma cases. In pseudoexfoliation glaucoma group, mean peripapillary retinal nerve fiber layer and ganglion cell complex thickness were statistically significantly lower in all quadrants compared to controls (p<0.001). Resistivity index values of the ophthalmic and central retinal arteries were significantly higher in pseudoexfoliation glaucoma group than in the controls (p<0.001 and r=0.684). Resistivity index values of the ophthalmic and central retinal arteries with ganglion cell complex thickness correlated significantly. On the other hand, no significant relationship for retinal nerve fiber layer thickness was identified. Conclusions: Structural changes (ganglion cell complex and ganglion cell inner plexiform layer) in patients with pseudoexfoliation glaucoma and early glaucomatous loss showed a significant correlation with changes in ocular vascular hemodynamics. In cases where systemic vascular resistance is increased, ganglion cell complex and ganglion cell inner plexiform layer may not exactly reflect glaucoma state. In such cases, thickness changes in the retinal nerve fiber layer may give more realistic results regarding glaucoma. We have seen that pseudoexfoliation glaucoma-induced structural deterioration and increased resistance in ocular hemodynamics correlated with ganglion cell complex, but not retinal nerve fiber layer.

RESUMO Objetivo: Investigar a correlação entre a hemodi­nâmica arterial, medida pela ultrassonografia com Doppler colorido, e os parâmetros de microarquitetura da retina, determinados pela tomografia de coerência óptica de domínio espectral (SD-OCT) no glaucoma pseudoexfoliativo. Métodos: Foram incluídos 82 participantes neste estudo prospectivo. Foram medidos os valores da camada de fibras nervosas da retina peripapilar, da camada plexiforme interna de células ganglionares e do complexo de células ganglionares. Os fluxos da artéria oftálmica e da artéria central da retina foram avaliados com ultrassonografia por Doppler colorida e foram calculados os valores do índice de resistividade. Resultados: Foram incluídos no estudo 47 casos de controle e 35 casos de glaucoma pseudoexfoliativo. No grupo com glaucoma pseudoexfoliativo, a média da camada de fibras nervosas da retina peripapilar e a espessura do complexo de células ganglionares foram menores em todos os quadrantes em comparação com os controles, com significância estatística (p<0,001). Os valores do índice de resistividade das artérias oftálmica e central da retina foram significativamente maiores no grupo com glaucoma pseudoexfoliativo que nos controles (p<0,001 e r=0,684). Ao se compararem os valores do índice de resistividade das artérias oftálmica e central da retina com a espessura do complexo de células ganglionares, foi encontrada uma correlação significativa entre elas. Por outro lado, não detectamos uma relação significativa para a espessura da camada de fibras nervosas da retina. Conclusões: Alterações estruturais (complexo de células ganglionares, camada plexiforme interna de células ganglionares) em pacientes com glaucoma pseudoexfoliativo com perda glaucomatosa precoce mostraram uma correlação significativa com alterações na hemodinâmica vascular ocular. Nos casos em que a resistência vascular sistêmica é aumentada, o complexo de células ganglionares e a camada plexiforme interna de células ganglionares podem não refletir exatamente o estado do glaucoma. Nesses casos, alterações na espessura da camada de fibras nervosas da retina podem dar resultados mais realistas em relação ao glaucoma. Observou-se uma correlação da deterioração estrutural induzida pelo glaucoma pseudoexfoliativo e do aumento da resistência na hemodinâmica ocular com o complexo de células ganglionares, mas não com a camada de fibras nervosas da retina.

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Slit-Robo signaling regulates midline crossing of commissural axons in different systems. In zebrafish, all retinofugal axons cross at the optic chiasm to innervate the contralateral tectum. Here, the mutant for the Robo2 receptor presents severe axon guidance defects, which were not completely reproduced in a Slit2 ligand null mutant. Since slit3 is also expressed around this area at the stage of axon crossing, we decided to analyze the possibility that it collaborates with Slit2 in this process. We found that the disruption of slit3 expression by sgRNA-Cas9 injection caused similar, albeit slightly milder, defects than those of the slit2 mutant, while the same treatment in the slit2-/-mz background caused much more severe defects, comparable to those observed in robo2 mutants. Tracking analysis of in vivo time-lapse experiments indicated differential but complementary functions of these secreted factors in the correction of axon turn errors around the optic chiasm. Interestingly, RT-qPCR analysis showed a mild increase in slit2 expression in slit3-deficient embryos, but not the opposite. Our observations support the previously proposed "repulsive channel" model for Slit-Robo action at the optic chiasm, with both Slits acting in different manners, most probably relating to their different spatial expression patterns.

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Objetivo: Determinar las características clínico-epidemiológicas de los pacientes diagnosticados con lesiones compresivas de la vía visual anterior. Métodos: Se realizó un estudio descriptivo transversal durante el período comprendido entre mayo de 2018 y marzo de 2020 con 41 pacientes con diagnóstico de síndrome compresivo de la vía visual anterior atendidos en el Servicio de Neuroftalmología del Instituto Cubano de Oftalmología "Ramón Pando Ferrer". Resultados: La mayor frecuencia en cuanto a síntomas fue la disminución progresiva de la visión central. Se encontraron lesiones de tipo tumoral en 39 pacientes para el 95,1 por ciento. Los defectos hemianópticos se detectaron en el campo visual del 45 por ciento de la muestra y el 33 por ciento presentó disminución difusa de la sensibilidad retiniana. Conclusiones: La mayoría de los pacientes fueron del sexo femenino en edades medias de la vida. Predominaron las lesiones tumorales sobre las vasculares. Los macroadenomas de hipófisis y los meningiomas fueron las etiologías más frecuentes y el sitio de compresión más encontrado fue el quiasma óptico. Se detectó disminución del grosor del complejo de células ganglionares maculares en la tomografía de coherencia óptica de la mayoría de los enfermos(AU)

Objective: To determine the clinical-epidemiological characteristics of patients diagnosed with compressive lesions of the anterior visual pathway. Methods: A cross-sectional descriptive study was conducted during the period from May 2018 to March 2020 with 41 patients diagnosed with compressive syndrome of the anterior visual pathway attended at the Neurophthalmology Service of the Cuban Institute of Ophthalmology "Ramón Pando Ferrer". Results: The most frequent symptom was the progressive decrease of central vision. Tumor type lesions were found in 39 patients for 95.1 percent. Hemianoptic defects were detected in the visual field of 45 percent of the sample and 33 percent presented diffuse decrease of retinal sensitivity. Conclusions: The majority of patients were female at middle ages of life. Tumor lesions predominated over vascular lesions. Pituitary macroadenomas and meningiomas were the most frequent etiologies and the most frequent site of compression was the optic chiasm. Decreased thickness of the macular ganglion cell complex was detected in the optical coherence tomography of most of the patients(AU)

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Introduction: Age-related macular degeneration (AMD) is the leading cause of irreversible central vision loss in developed countries and one of the leading causes of blindness. In this work, we evaluated color vision and the pupil light reflex (PLR) to assess visual function in patients with early and neovascular AMD (NVAMD) compared with the control group. Methods: We recruited 34 early patients with dry AMD and classified them into two groups following AREDS: 13 patients with NVAMD and 24 healthy controls. Controls and patients with early dry AMD had visual acuity (VA) best or equal to 20/25 (0.098 logMAR). Color vision was assessed in controls and patients with early dry AMD using the Cambridge Color Test (CCT) 2.0 through the Trivector protocol. The PLR was evaluated using a Ganzfeld, controlled by the RETI-port system. The stimuli consisted of 1s blue (470 nm) and red (631 nm) light flashes presented alternately at 2-min intervals. To assess the cone contribution, we used a red flash at 2.4 log cd.m-2, with a blue background at 0.78 log cd.m-2. For rods, we used 470-nm flashes at -3 log cd.m-2, and for the melanopsin function of ipRGCs, we used 470 nm at 2.4 log cd.m-2. Results: Patients with early dry AMD had reduced color discrimination in all three axes: protan (p = 0.0087), deutan (p = 0.0180), and tritan (p = 0.0095) when compared with the control group. The PLR has also been affected in patients with early dry AMD and patients with NVAMD. The amplitude for the melanopsin-driven response was smaller in patients with early dry AMD (p = 0.0485) and NVAMD (p = 0.0035) than in the control group. The melanopsin function was lower in patients with NVAMD (p = 0.0290) than the control group. For the rod-driven response, the latency was lower in the NVAMD group (p = 0.0041) than in the control group. No changes were found in cone-driven responses between the control and AMD groups. Conclusion: Patients with early dry AMD present diffusely acquired color vision alteration detected by CCT. Rods and melanopsin contributions for PLR are affected in NVAMD. The CCT and the PLR may be considered sensitive tests to evaluate and monitor functional changes in patients with AMD.

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Glaucoma is one of the world's most frequent visual impairment causes and leads to selective damage to retinal ganglion cells and their axons. Despite glaucoma's most accepted risk factor is increased intraocular pressure (IOP), the mechanisms behind the disease have not been fully elucidated. To date, IOP lowering remains the gold standard; however, glaucoma patients may still lose vision regardless of effective IOP management. Therefore, the exclusive IOP control apparently is not enough to stop the disease progression, and developing new resources to protect the retina and optic nerve against glaucoma is a goal of vast clinical importance. Besides pharmacological treatments, environmental conditions have been shown to prevent neurodegeneration in the central nervous system. In this review, we discuss current concepts on key pathogenic mechanisms involved in glaucoma, the effect of enriched environment on these mechanisms in different experimental models, as well as recent evidence supporting the preventive and therapeutic effect of enriched environment exposure against experimental glaucomatous damage. Finally, we postulate that stimulating vision may become a non-invasive and rehabilitative therapy that could be eventually translated to the human disease, preventing glaucoma-induced terrible sequelae resulting in permanent visual disability.

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Ouabain is a classic Na+K+ATPase ligand and it has been described to have neuroprotective effects on neurons and glial cells at nanomolar concentrations. In the present work, the neuroprotective and immunomodulatory potential of ouabain was evaluated in neonatal rat retinal cells using an optic nerve axotomy model in vitro. After axotomy, cultured retinal cells were treated with ouabain (3 nM) at different periods. The levels of important inflammatory receptors in the retina such as TNFR1/2, TLR4, and CD14 were analyzed. We observed that TNFR1, TLR4, and CD14 were decreased in all tested periods (15 min, 45 min, 24 h, and 48 h). On the other hand, TNFR2 was increased after 24 h, suggesting an anti-inflammatory potential for ouabain. Moreover, we showed that ouabain also decreased Iba-1 (microglial marker) density. Subsequently, analyses of retrograde labeling of retinal ganglion cells (RGC) were performed after 48 h and showed that ouabain-induced RGC survival depends on autophagy. Using an autophagy inhibitor (3-methyladenine), we observed a complete blockage of the ouabain effect. Western blot analyses showed that ouabain increases the levels of autophagy proteins (LC3 and Beclin-1) coupled to p-CREB transcription factor and leads to autophagosome formation. Additionally, we found that the ratio of cleaved/pro-caspase-3 did not change after ouabain treatment; however, p-JNK density was enhanced. Also, ouabain decreased reactive oxygen species production immediately after axotomy. Taken together, our results suggest that ouabain controls neuroinflammation in the retina following optic nerve axotomy and promotes RGC neuroprotection through activation of the autophagy pathway.

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Gangliosides are glycosphingolipids abundantly expressed in the vertebrate nervous system, and are classified into a-, b-, or c-series according to the number of sialic acid residues. The enzyme GD3 synthase converts GM3 (an a-series ganglioside) into GD3, a b-series ganglioside highly expressed in the developing and adult retina. The present study evaluated the visual system of GD3 synthase knockout mice (GD3s-/- ), morphologically and functionally. The absence of b- series gangliosides in the retinas of knockout animals was confirmed by mass spectrometry imaging, which also indicated an accumulation of a-series gangliosides, such as GM3. Retinal ganglion cell (RGC) density was significantly reduced in GD3s-/- mice, with a similar reduction in the number of axons in the optic nerve. Knockout animals also showed a 15% reduction in the number of photoreceptor nuclei, but no difference in the bipolar cells. The area occupied by GFAP-positive glial cells was smaller in GD3s-/- retinas, but the number of microglial cells/macrophages did not change. In addition to the morphological alterations, a 30% reduction in light responsiveness was detected through quantification of pS6-expressing RGC, an indicator of neural activity. Furthermore, electroretinography (ERG) indicated a significant reduction in RGC and photoreceptor electrical activity in GD3s-/- mice, as indicated by scotopic ERG and pattern ERG (PERG) amplitudes. Finally, evaluation of the optomotor response demonstrated that GD3s-/- mice have reduced visual acuity and contrast sensitivity. These results suggest that b-series gangliosides play a critical role in regulating the structure and function of the mouse visual system.

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Interleukin-2 (IL-2) is a classical pro-inflammatory cytokine known to display neuroprotective roles in the central nervous system including the retina. In the present study, we investigate the molecular targets involved in the neurotrophic effect of IL-2 on retinal ganglion cells (RGC) after optic nerve axotomy. Analysis of retrograde labeling of RGC showed that common cell survival mediators, as Trk receptors, Src, PI3K, PKC, and intracellular calcium do not mediate the neurotrophic effect of IL-2 on RGC. No involvement of MAPK p38 was also observed. However, other MAPKs as MEK and JNK appear to be mediating this IL-2 effect. Our data also indicate that JAK2/3 are important intracellular proteins for the IL-2 effect. Interestingly, we demonstrate that the IL-2 effect depends on dopamine D1 receptors (D1R), the cAMP/PKA pathway, interleukin-10 (IL-10), and NF-κB, suggesting that RGC survival induced by IL-2 encompasses a molecular network of major complexity. In addition, treatment of retinal cells with recombinant IL-10 or 6-Cl-pb (D1R full agonist) was able to increase RGC survival similar to IL-2. Taken together, our results suggest that after optic nerve axotomy, the increase in RGC survival triggered by IL-2 is mediated by IL-10 and D1R along with the intracellular pathways of MAPKs, JAK/STAT, and cAMP/PKA.

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BACKGROUND: Alzheimer's disease (AD) is the most prevalent form of dementia worldwide. This neurodegenerative syndrome affects cognition, memory, behavior, and the visual system, particularly the retina. OBJECTIVE: This work aims to determine whether the 5xFAD mouse, a transgenic model of AD, displays changes in the function of retinal ganglion cells (RGCs) and if those alterations are correlated with changes in the expression of glutamate and gamma-aminobutyric acid (GABA) neurotransmitters. METHODS: In young (2-3-month-old) and adult (6-7-month-old) 5xFAD and WT mice, we have studied the physiological response, firing rate, and burst of RGCs to various types of visual stimuli using a multielectrode array system. RESULTS: The firing rate and burst response in 5xFAD RGCs showed hyperactivity at the early stage of AD in young mice, whereas hypoactivity was seen at the later stage of AD in adults. The physiological alterations observed in 5xFAD correlate well with an increase in the expression of glutamate in the ganglion cell layer in young and adults. GABA staining increased in the inner nuclear and plexiform layer, which was more pronounced in the adult than the young 5xFAD retina, altering the excitation/inhibition balance, which could explain the observed early hyperactivity and later hypoactivity in RGC physiology. CONCLUSION: These findings indicate functional changes may be caused by neurochemical alterations of the retina starting at an early stage of the AD disease.

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PURPOSE: In this study, we aimed to determine whether or not COM leads to loss of spiral and Scarpa ganglion neurons. METHODS: From the human temporal bone (HTB) collection at the University of Minnesota we selected human temporal bones with COM, defined as the presence of clinically intractable tissue abnormalities in the middle ear (cholesteatoma, perforation of the eardrum, granulation tissue, fibrosis, tympanosclerosis, and cholesterol granuloma). We also selected HTBs from donors with no ear diseases as controls. We quantitatively analyzed the number of spiral and Scarpa ganglion cells and compared the results obtained in the control and study groups. RESULTS: In both COM and control groups we observed a significant negative correlation between age and number of both spiral (R = -0.632; P < 0.001; 95% CI - 0.766 to - 0.434) and Scarpa ganglion (R = - 0.404; P = 0.008; 95% CI - 0.636 to - 0.051) cells. We did not find any significant differences in the number of spiral ganglion cells (in total or per segment) or in the density of Scarpa ganglion cells (in each vestibular nerve or both) in the COM group as compared with controls (P > 0.05). CONCLUSIONS AND RELEVANCE: Our results did not demonstrate significant loss of cochlear or vestibular peripheral ganglion neuron loss in HTBs with COM as compared with controls.

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Neurovespina is a synthetic peptide modified from Occidentalin-1202, a nine amino acid residue peptide isolated from the venom of the social wasp Polybia occidentalis. Previous studies showed that this peptide has a neuroprotective effect on the central nervous system, but its action on the eye has not been explored. So, the objective of this work was to investigate the neuroprotective effect of Neurovespina on the retina and its angiogenic potential in the chicken chorioallantoic membrane (CAM). Retinal ischemia was induced in rats by acute elevation of intraocular pressure (IOP). Electroretinography (ERG) measurements, histopathological and immunohistochemical analysis, and transmission electronic microscopy (TEM) records were performed to check the neuroprotection effect of Neurovespina in the retina of the animals. The angiogenic activity of the peptide was investigated by CAM assay. The results showed that Neurovespina was able to reduce the effects induced by ischemic injury, preventing the reduction of a- and b-waves in the scotopic ERG. Histopathological and immunohistochemistry assays showed that Neurovespina, mainly at 60 µg/ml, protected all layers of the retina. The CAM assay revealed that the peptide promoted the reduction of CAM vessels. So, Neurovespina was able to protect retinal cells from ischemic insult and has an antiangiogenic effect, which can be considered as a promising neuroprotective agent for intravitreal application.

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El glaucoma es una neuropatía óptica caracterizada por la pérdida de células ganglionares de la retina y sus axones. Constituye la primera causa de ceguera irreversible a nivel mundial; por lo tanto, la detección oportuna y el monitoreo continuo es de vital importancia. El grosor de la capa de la fibra nerviosa retiniana circumpapilar, medido mediante tomografía de coherencia óptica, es la principal estrategia de evaluación estructural utilizada en el diagnóstico del glaucoma. Sin embargo, considerando que la mácula es el área retiniana relacionada con la visión central y contiene el 50 por ciento de las células ganglionares de la retina, medir el grosor macular parece ser una buena opción para detectar precozmente la muerte de estas células. En esta revisión exponemos los antecedentes, la justificación anatómica, los protocolos y los principales artefactos de la tomografía de coherencia óptica macular en la atención del glaucoma. Además, ofrecemos un enfoque actualizado sobre cómo usar estas exploraciones en la práctica clínica(AU)

Glaucoma is an optic neuropathy characterized by the loss of retinal ganglion cells and their axons. It is the leading cause of irreversible blindness worldwide, hence the crucial importance of its timely detection and continuous monitoring. Optical coherence tomography measurement of circumpapillary retinal nerve fiber layer thickness is the main structural evaluation strategy to diagnose glaucoma. However, in view that the macula is the retinal area related to central vision and contains 50 percent of the retinal ganglion cells, measuring macular thickness seems to be a good option for early detection of the death of these cells. The present review discusses the antecedents, anatomical justification, protocols and main artifacts of macular optical coherence tomography as related to the care of glaucoma. An updated approach is also provided to the way these explorations may be used in clinical practice(AU)

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RESUMO

RESUMEN El glaucoma es una neuropatía óptica caracterizada por la pérdida de células ganglionares de la retina y sus axones. Se presentan dos casos clínicos, ambos miopes con sospecha de glaucoma, con el objetivo de valorar la importancia del análisis de las células ganglionares en el diagnóstico de estos pacientes. La evaluación de los cambios estructurales glaucomatosos en los ojos miopes es difícil, por las considerables variaciones morfológicas en la cabeza del nervio óptico y otras estructuras del segmento posterior del ojo. La tomografía de coherencia óptica permite el análisis cuantitativo in vivo del disco óptico, la capa de fibras nerviosas de la retina y el área macular; pero interpretar los hallazgos en ojos miopes, y especialmente en altos miopes, puede ser un verdadero desafío. Estudios recientes han demostrado que las mediciones maculares tienen ventajas sobre el análisis de la capa de fibras nerviosas de la retina para determinar si los defectos del grosor de la retina se relacionan con el glaucoma o con la miopía. Sin embargo, se deben considerar varios estudios en el intento de emitir un diagnóstico de certeza(AU)

ABSTRACT Glaucoma is an optic neuropathy characterized by the loss of retinal ganglion cells and their axons. Two cases are presented, both myopic and with suspected glaucoma, with the purpose of assessing the role of ganglion cell analysis in their diagnosis. Evaluation of structural glaucomatous changes in myopic eyes is a difficult task, due to the considerable morphological variations occurring in the optic nerve head and other structures from the posterior segment of the eye. Optical coherence tomography allows in vivo quantitative analysis of the optic disc, the retinal nerve fiber layer, and the macular area, but interpreting the findings in myopic eyes, particularly in highly myopic eyes, may be a real challenge. Recent studies have shown that macular measurements have advantages over retinal nerve fiber layer analysis to determine whether the retinal thickness defects are related to glaucoma or to myopia. However, several studies should be considered in the attempt to reach an accurate diagnosis(AU)

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