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Glaucoma is marked by a progressive degeneration of the optic nerve and delayed loss of retinal ganglion cells (RGCs), the projection neurons of the eye. Because RGCs are not replaced and because surviving RGCs cannot regenerate their axons, the visual loss in glaucoma is largely irreversible. Here we describe methods to evaluate treatments that may be beneficial for treating glaucoma using in vitro cell culture models (immunopanning to isolate neonatal RGCs, dissociated mature retinal neurons, retinal explants) and in vivo models that test potential treatments or investigate underlying molecular mechanisms in an intact system. Potentially, the use of these models can help investigators continue to improve treatments to preserve RGCs and restore visual function in patients with glaucoma.
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Sobrevivência Celular , Regeneração Nervosa , Nervo Óptico , Células Ganglionares da Retina , Células Ganglionares da Retina/fisiologia , Animais , Regeneração Nervosa/fisiologia , Nervo Óptico/fisiologia , Glaucoma/fisiopatologia , Glaucoma/patologia , Camundongos , Ratos , Técnicas de Cultura de Células/métodos , Células CultivadasRESUMO
Recent technological advances in single-cell RNA sequencing (scRNA-Seq) have enabled scientists to answer novel questions in biology with unparalleled precision. Indeed, in the field of ocular development and regeneration, scRNA-Seq studies have resulted in a number of exciting discoveries that have begun to revolutionize the way we think about these processes. Despite the widespread success of scRNA-Seq, many scientists are wary to perform scRNA-Seq experiments due to the uncertainty of obtaining high-quality viable cell populations that are necessary for the generation of usable data that enable rigorous computational analyses. Here, we describe methodology to reproducibility generate high-quality single-cell suspensions from embryonic zebrafish eyes. These single-cell suspensions served as inputs to the 10× Genomics v3.1 system and yielded high-quality scRNA-Seq data in proof-of-principle studies. In describing methodology to quantitatively assess cell yields, cell viability, and other critical quality control parameters, this protocol can serve as a useful starting point for others in designing their scRNA-Seq experiments in the zebrafish eye and in other developing or regenerating tissues in zebrafish or other model systems.
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Retina , Análise de Sequência de RNA , Análise de Célula Única , Peixe-Zebra , Animais , Peixe-Zebra/genética , Peixe-Zebra/embriologia , Análise de Célula Única/métodos , Retina/citologia , Retina/embriologia , Retina/metabolismo , Análise de Sequência de RNA/métodos , Separação Celular/métodosRESUMO
The generation of quality data from a single-nucleus profiling experiment requires nuclei to be isolated from tissues in a gentle and efficient manner. Nuclei isolation must be carefully optimized across tissue types to preserve nuclear architecture, prevent nucleic acid degradation, and remove unwanted contaminants. Here, we present an optimized workflow for generating a single-nucleus suspension from ocular tissues of the embryonic chicken that is compatible with various downstream workflows. The described protocol enables the rapid isolation of a high yield of aggregate-free nuclei from the embryonic chicken eye without compromising nucleic acid integrity, and the nuclei suspension is compatible with single-nucleus RNA and ATAC sequencing. We detail several stopping points, either via cryopreservation or fixation, to enhance workflow adaptability. Further, we provide a guide through multiple QC points and demonstrate proof-of-principle using two commercially available kits. Finally, we demonstrate that existing in silico genotyping methods can be adopted to computationally derive biological replicates from a single pool of chicken nuclei, greatly reducing the cost of biological replication and allowing researchers to consider sex as a variable during analysis. Together, this tutorial represents a cost-effective, simple, and effective approach to single-nucleus profiling of embryonic chicken eye tissues and is likely to be easily modified to be compatible with similar tissue types.
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Núcleo Celular , Galinhas , Análise de Célula Única , Animais , Núcleo Celular/metabolismo , Núcleo Celular/genética , Embrião de Galinha , Análise de Célula Única/métodos , Olho/embriologia , Olho/metabolismo , Criopreservação/métodos , Sequenciamento de Cromatina por Imunoprecipitação/métodosRESUMO
Retinal degenerative diseases including age-related macular degeneration and glaucoma are estimated to currently affect more than 14 million people in the United States, with an increased prevalence of retinal degenerations in aged individuals. An expanding aged population who are living longer forecasts an increased prevalence and economic burden of visual impairments. Improvements to visual health and treatment paradigms for progressive retinal degenerations slow vision loss. However, current treatments fail to remedy the root cause of visual impairments caused by retinal degenerations-loss of retinal neurons. Stimulation of retinal regeneration from endogenous cellular sources presents an exciting treatment avenue for replacement of lost retinal cells. In multiple species including zebrafish and Xenopus, Müller glial cells maintain a highly efficient regenerative ability to reconstitute lost cells throughout the organism's lifespan, highlighting potential therapeutic avenues for stimulation of retinal regeneration in humans. Here, we describe how the application of single-cell RNA-sequencing (scRNA-seq) has enhanced our understanding of Müller glial cell-derived retinal regeneration, including the characterization of gene regulatory networks that facilitate/inhibit regenerative responses. Additionally, we provide a validated experimental framework for cellular preparation of mouse retinal cells as input into scRNA-seq experiments, including insights into experimental design and analyses of resulting data.
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Células Ependimogliais , Retina , Análise de Célula Única , Animais , Camundongos , Análise de Célula Única/métodos , Retina/metabolismo , Células Ependimogliais/metabolismo , Regeneração/genética , Análise de Sequência de RNA/métodos , Degeneração Retiniana/genética , Degeneração Retiniana/terapia , RNA-Seq/métodos , Modelos Animais de DoençasRESUMO
Various strategies for replacing retinal neurons lost in degenerative diseases are under investigation, including stimulating the endogenous regenerative capacity of Müller Glia (MG) as injury-inducible retinal stem cells. Inherently regenerative species, such as zebrafish, have provided key insights into mechanisms regulating MG dedifferentiation to a stem-like state and the proliferation of MG and MG-derived progenitor cells (MGPCs). Interestingly, promoting MG/MGPC proliferation is not sufficient for regeneration, yet mechanistic studies are often focused on this measure. To fully account for the regenerative process, and facilitate screens for factors regulating cell regeneration, an assay for quantifying cell replacement is required. Accordingly, we adapted an automated reporter-assisted phenotypic screening platform to quantify the pace of cellular regeneration kinetics following selective cell ablation in larval zebrafish. Here, we detail a method for using this approach to identify chemicals and genes that control the rate of retinal cell regeneration following selective retinal cell ablation.
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Peixe-Zebra , Animais , Retina/citologia , Retina/metabolismo , Fenótipo , Proliferação de Células , Regeneração , Células Ependimogliais/citologia , Células Ependimogliais/metabolismo , Células-Tronco/citologia , Células-Tronco/metabolismo , Cinética , Regeneração Nervosa/fisiologiaRESUMO
Retinal degenerative diseases are a leading cause of vision loss and blindness globally, impacting millions. These diseases result from progressive damage to retinal pigment epithelial (RPE) cells for which no curative or palliative treatments exist. Cell therapy, particularly RPE transplantation, has emerged as a promising strategy for vision restoration. This review provides a comprehensive overview of the recent advancements in clinical trials related to RPE transplantation. We discuss scaffold-free and scaffold-based approaches, including RPE cell suspensions and pre-organized RPE monolayers on biomaterial scaffolds. Key considerations, such as the form and preparation of RPE implants, delivery devices, strategies, and biodegradability of scaffolds, are examined. The article also explores the challenges and opportunities in RPE scaffold development, emphasising the crucial need for functional integration, immunomodulation, and long-term biocompatibility to ensure therapeutic efficacy. We also highlight ongoing efforts to optimise RPE transplantation methods and their potential to address retinal degenerative diseases.
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Degeneração Retiniana , Epitélio Pigmentado da Retina , Humanos , Epitélio Pigmentado da Retina/transplante , Epitélio Pigmentado da Retina/citologia , Epitélio Pigmentado da Retina/metabolismo , Degeneração Retiniana/terapia , Animais , Alicerces Teciduais/químicaRESUMO
Artificial intelligence (AI) is reshaping ophthalmology by enhancing diagnostic precision and treatment strategies, particularly in retinal disorders and pediatric ophthalmology. This review examines AI's efficacy in diagnosing conditions such as diabetic retinopathy (DR) and age-related macular degeneration (AMD) using imaging techniques, such as optical coherence tomography (OCT) and fundus photography. AI also shows promise in pediatric care, aiding in the screening of retinopathy of prematurity (ROP) and the management of conditions, including pediatric cataracts and strabismus. However, the integration of AI in ophthalmology presents challenges, including ethical concerns regarding algorithm biases, privacy issues, and limitations in data set quality. Addressing these challenges is crucial to ensure AI's responsible and effective deployment in clinical settings. This review synthesizes current research, underscoring AI's transformative potential in ophthalmology while highlighting critical considerations for its ethical use and technological advancement.
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AIM: To determine the effects of the first-dose administration of the Sinovac vaccine on the retina, choroid, and optic disc in healthy participants. METHODS: This prospective design study was conducted with 27 healthy healthcare workers who received the first dose of Sinovac vaccine and 25 healthy controls who were not vaccinated. In the vaccinated group, ophthalmological examinations and measurements were performed before vaccination and one week and one month after vaccination. Subfoveal, nasal, and temporal choroidal thicknesses (CTs), retinal nerve fiber layer (RNFL) thickness, and macular thickness (MT) were determined using spectral domain-optical coherence tomography at all visits. Superficial, deep, and peripapillary radial capillary plexus (superficial capillary plexus, deep capillary plexus (DCP), and radial peripapillary capillary, respectively), choriocapillaris vascular density, and foveal avascular zone parameters were measured on optical coherence tomography-angiography (OCT-A). RESULTS: No significant difference was detected between the two groups in terms of the parameters measured by OCT and OCT-A (p > 0.05 for all). The CT values measured in all quadrants were significantly higher at the first week after vaccination (p < 0.05 for all), and they returned to their pre-vaccination values at the first month post-vaccination measurement (p > 0.05 for all). Concerning the RNFL and MT values, there was no significant difference between the pre-vaccination and post-vaccination first-week measurements (p > 0.05 for all), but a statistically significant increase was detected in the post-vaccination first-month MT and RNFL measurements (p < 0.05 for all). Only the decreases in the foveal DCP and choriocapillaris vascular density values were significant at the first week after vaccination (p < 0.05 for all). CONCLUSION: The early changes detected after vaccination in this study suggest the possibility that autoimmune, vascular, and inflammatory diseases may simultaneously emerge in the early post-vaccination period or may be triggered after vaccination, or that the vaccine may unmask these diseases.
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AIMS: To evaluate the visual function and foveal architecture in patients with stage 3 idiopathic epiretinal membrane (iERM). METHODS: A cross-sectional observational study included 56 eyes of 52 patients with stage 3 iERM. The patients were classified into type A ectopic inner foveal layers (EIFL) and type B EIFL based on the presence of a continuous hyporeflective band. Visual function and foveal microarchitecture were assessed in enrolled eyes. Best-corrected visual acuity (BCVA), metamorphopsia scores, retinal sensitivity and optical coherence tomography (OCT)/OCT angiography features were compared between two subtypes. RESULT: The BCVA in type A EIFL and type B EIFL was 0.22 logarithm of minimal angle of resolution (logMAR) (0.15 logMAR, 0.40 logMAR) and 0.53±0.23 logMAR, respectively (p=0.002). Type B EIFL had higher average metamorphopsia scores, especially horizontal metamorphopsia scores, than type A (p=0.013, p=0.007, respectively). Type B EIFL had worse central 2° foveal sensitivity than type A (p=0.034). Type B EIFL had thicker central foveal thickness and EIFL thickness (514.08±73.80 µm vs 444.41±56.57 µm, p=0.001; 159.75±78.30 µm vs 48.44±18.37 µm, p<0.0001; respectively). The foveal avascular zone area of type B EIFL was smaller than that of type A (0.042±0.022 mm2 vs 0.077±0.039 mm2, p<0.0001). The vessel density and flow area of the superficial vascular complex in type B EIFL were larger than those in type A (both p=0.001). CONCLUSIONS: Type B EIFL demonstrated significantly worse visual function than type A EIFL, along with marked differences in foveal microstructure and microvasculature. Our study complements the current staging of iERM and helps determine the optimal timing of iERM surgery.
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Retinal hypoxia stands as a pivotal yet often underappreciated factor in the etiology and progression of many retinal disorders such as glaucoma, hypertensive retinopathy, diabetic retinopathy, retinal vein occlusions, and retinal artery occlusions. Current treatment methodologies fail to directly address the underlying pathophysiology of hypoxia and aim to improve ischemia through alternative methods. In this review, we discuss the critical role of retinal hypoxia in the pathogenesis of various retinal diseases and highlight the need for innovative therapeutic strategies that address the root cause of these conditions. As our understanding of retinal hypoxia continues to evolve, the emergence of new technologies holds the promise of more effective treatments, offering hope to patients at risk of vision loss.
A review of old and new therapeutic strategies for addressing oxygen deprivation in retinal diseases This paper talks about how lack of oxygen in the retina can cause different eye diseases like glaucoma, diabetic retinopathy, and retinal artery occlusions. It explains how our current treatments don't directly fix this lack of oxygen, but rather try to help in other ways. The paper also discusses the science behind why these diseases happen and what happens in the eye when there's not enough oxygen. Ultimately, we finish our discussion with an overview of novel technology that are currently being used in other fields and could be applied in these eye disorders.
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BACKGROUND/AIMS: To determine if patients with vitreoretinal lymphoma (VRL) and concomitant central nervous system lymphoma (CNSL) may present without brain MRI findings, but possess cerebrospinal fluid (CSF) suspicious for lymphoma. METHODS: This was a retrospective, single-centre, observational study evaluating patients with a diagnosis or suspicion of VRL seen at Memorial Sloan Kettering Cancer Center between 2006 and 2024. Patients were included if the final diagnosis was biopsy-proven CNSL and both MRI brain with and without contrast±CSF evaluation (obligatory for inclusion if MRI negative) were performed at the initial diagnostic workup. Patients were excluded if CNS disease treatment (brain, spine or CSF) preceded ocular disease. Patients with prior extra-CNS disease were included. Clinical records and radiographic imaging were retrospectively reviewed and relevant data were recorded for each patient. We evaluated the proportion of patients with MRI negative and CSF suspicious for lymphoma. Subgroup analysis included imaging features, pathology, treatment and disease course. RESULTS: We identified 65 patients. Of the 65 patients at the presentation of VRL, 30 had negative MRI brain and CSF, 16 had positive brain MRI and negative CSF and 8 had both positive MRI brain and CSF. 11 (16.9%) had CSF suspicious for lymphoma without positive findings on MRI of the brain. In this subgroup, the median age was 66 years (range 49-82) and 36% were female. 86% of these patients were asymptomatic neurologically. 73% underwent systemic treatment. At a mean 3 years follow-up, 91% of patients were living. CONCLUSION: In patients with suspected VRL, it is possible to have CSF test positive for lymphoma in the context of negative brain MRI. This suggests, when evaluating VRL patients for concomitant CNS disease, CSF evaluation leads to earlier detection and systemic treatment, even when MRI brain findings are negative. In our cohort, an absence of CSF evaluation in the context of negative brain MRI could have missed 16.9% of patients with CNS lymphoma.
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Neuropeptide cocaine- and amphetamine-regulated transcript (CART) is widely expressed in the brains of teleosts, amphibians, birds, and mammals and has emerged as a conserved regulator of energy balance across these vertebrate phyla. However, as yet, there is no information on CART in the reptilian brain. We characterized the cDNA encoding CART and mapped CART-containing elements in the brain of gecko, Hemidactylus leschenaultii (hl) using a specific anti-CART antiserum. We report a 683-bp hlcart transcript containing a 336-bp open reading frame, which encodes a putative 111-amino acid hl-preproCART. The 89-amino acid hl-proCART generated from hl-preproCART produced two putative bioactive hl-CART-peptides. These bioactive CART-peptides were > 93% similar with those in rats/humans. Although reverse transcription-polymerase chain reaction (RT-PCR) detected hlcart-transcript in the brain, CART-containing neurons/fibers were widely distributed in the telencephalon, diencephalon, mesencephalon, rhombencephalon, spinal cord, and retina. The mitral cells in olfactory bulb, neurons in the paraventricular, periventricular, arcuate (Arc), Edinger-Westphal, and brainstem nuclei were intensely CART-positive. In view of antagonistic roles of neuropeptide Y (NPY) and CART in energy balance in the framework of mammalian hypothalamus, we probed CART-NPY interaction in the hypothalamus of H. leschenaultii. Double immunofluorescence showed a dense NPY-innervation of Arc CART neurons. Ex vivo hypothalamic slices treated with NPY/NPY-Y1-receptor agonist significantly reduced hlcart-mRNA levels in the Arc-containing tissues and CART-ir in the dorsal-Arc. However, CART-ir in ventral-Arc was unaffected. NPY via Y1-receptors may regulate energy balance by inhibiting dArc CART neurons. This study on CART in a reptilian brain fills the current void in literature and underscores the conserved feature of the neuropeptide across the entire vertebrate phyla.
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Lagartos , Proteínas do Tecido Nervoso , Neuropeptídeo Y , Animais , Neuropeptídeo Y/metabolismo , Neuropeptídeo Y/genética , Proteínas do Tecido Nervoso/metabolismo , Proteínas do Tecido Nervoso/genética , Lagartos/metabolismo , Sequência de Aminoácidos , Encéfalo/metabolismo , Sistema Nervoso Central/metabolismo , Neurônios/metabolismo , MasculinoRESUMO
PURPOSE: Astragalus polysaccharide (APS), a water-soluble heteropolysaccharide, possesses immunomodulatory, anti-inflammatory, and cardioprotective properties. This study investigates the neuroprotective potential of APS in a model of N-Methyl-d-aspartic acid (NMDA)-induced retinal neurodegeneration, aiming to explore its potential as a treatment for retinal degenerative diseases. METHODS: Retinal function was evaluated using electroretinography (ERG), optomotor reflex (OMR), and flash visual evoked potentials (FVEP). Retinal inflammatory responses were examined through immunohistochemistry, western blotting (WB), and quantitative reverse transcription PCR (qRT-PCR). To assess the integrity of visual projections, an intravitreal injection of adeno-associated virus (AAV) was employed to trace the projections of retinal ganglion cells (RGCs) to the visual centers. RESULTS: APS treatment conferred protection to retinal cells, as indicated by ERG and OMR assessments. And APS intervention mitigated NMDA-induced apoptosis, evidenced by a decrease in TUNEL-positive cells. Furthermore, APS treatment attenuated the NMDA-induced reduction in RGC projections to the visual centers, including the superior colliculus and lateral geniculate nucleus, as demonstrated by AAV tracing. CONCLUSIONS: Our findings reveal that APS shields the retina from NMDA-induced damage by inhibiting the NF-κB signaling pathway and reduces the detrimental effects of NMDA on RGC projections to the visual centers. These findings propose APS as a potential novel therapeutic agent for the treatment of retinal diseases.
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PURPOSE: Abetalipoproteinemia (ABL, MIM 200,100) is a rare autosomal recessive disorder caused by nonfunctional microsomal triglyceride transfer protein leading to absence of apolipoprotein B-containing lipoproteins in plasma and a retinitis pigmentosa-like fundus. The MTTP gene is expressed in retinal pigment epithelium (RPE) and ganglion cells of the human retina. Understanding ABL pathophysiology would benefit from new cellular-level clinical imaging of affected retinas. METHODS: We report multimodal retinal imaging in two patients with ABL. Case 1 (67-year-old woman) exhibited a bilateral decline of vision due to choroidal neovascularization (CNV) associated with angioid streaks and calcified Bruch membrane. Optical coherence tomography were consistent with basal laminar deposits and subretinal drusenoid deposits (SDD). RESULTS: Case 2 (46-year-old woman) exhibited unusual hyperpigmentation at the right fovea with count-fingers vision and a relatively unremarkable left fundus with 20/30 vision. The left eye exhibited the presence of nodular drusen and SDD and the absence of macular xanthophyll pigments. CONCLUSION: We propose that mutated MTTP within the retina may contribute to ABL retinopathy in addition to systemic deficiencies of fat-soluble vitamins. This concept is supported by a new mouse model with RPE-specific MTTP deficiency and a retinal degeneration phenotype. The observed range of human pathology, including angioid streaks, underscores the need for continued monitoring in adulthood, especially for CNV, a treatable condition.
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Central serous chorioretinopathy (CSCR) is a retinal disease characterised by the accumulation of subretinal fluid, which often resolves spontaneously in acute cases. However, approximately one-third of patients experience recurrences that may cause severe and irreversible vision. This study aimed to identify parameters derived from optical coherence tomography (OCT) that are associated with CSCR recurrence. Our dataset included 5211 OCT scans from 344 eyes of 255 patients diagnosed with CSCR. 178 eyes were identified as recurrent, 109 as non-recurrent, and 57 were excluded. We extracted parameters using artificial intelligence algorithms based on U-Nets, convolutional kernels, and morphological operators. We applied inferential statistics to evaluate differences between the recurrent and non-recurrent groups, and we used a logistic regression predictive model, reporting the coefficients as a measure of biomarker importance. We identified nine predictive biomarkers for CSCR recurrence: age, intraretinal fluid, subretinal fluid, pigment epithelial detachments, choroidal vascularity index, integrity of photoreceptors and retinal pigment epithelium layer, choriocapillaris and choroidal stroma thickness, and thinning of the outer nuclear layer, and of the inner nuclear layer combined with the outer plexiform layer. These results could enable future developments in the automatic detection of CSCR recurrence, paving the way for translational medical applications.
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Biomarcadores , Coriorretinopatia Serosa Central , Recidiva , Tomografia de Coerência Óptica , Humanos , Coriorretinopatia Serosa Central/diagnóstico por imagem , Coriorretinopatia Serosa Central/patologia , Coriorretinopatia Serosa Central/metabolismo , Coriorretinopatia Serosa Central/diagnóstico , Tomografia de Coerência Óptica/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Líquido Sub-Retiniano/metabolismo , Corioide/patologia , Corioide/diagnóstico por imagem , Corioide/metabolismo , Epitélio Pigmentado da Retina/patologia , Epitélio Pigmentado da Retina/metabolismo , Epitélio Pigmentado da Retina/diagnóstico por imagemRESUMO
PURPOSE: Glucagon-like peptide-1 receptor agonists (GLP-1RA) are used to treat type 2 diabetes mellitus (DM) by augmenting insulin release and sensitivity. We assessed the overall risk for development of vision-threatening diabetic retinopathy (VTDR), proliferative diabetic retinopathy (PDR), and diabetic macular edema (DME), among GLP-1RA users. METHODS: A retrospective cohort of patients with NPDR newly started on a GLP-1RA from a national insurance claims database was compared to a cohort of patients treated with other oral anti-diabetic agents and matched for age, sex, race, index year, and number of active diabetic medications. Exclusions occurred for < 2 years in the database before diagnosis; prior diagnoses of PDR, DME, vitreous hemorrhage, and/or other retinal vascular diseases; and prior intraocular treatment for VTDR. RESULTS: A total of 6093 users of GLP-1RA were matched to 14,122 controls. In the GLP-1RA cohort, 632 (10.1%), 76 (1.2%), and 544 (8.9%) patients progressed to VTDR, PDR, or DME, respectively. This is compared to 1332 (9.5%) VTDR, 165 (1.2%) PDR, or 1148 (8.1%) DME in the control group. Accounting for underlying DM severity with IPTW, no difference in hazard was seen in the GLP-1RA cohort compared to controls for progression to VTDR (HR = 1.02, 95%CI: 0.92-1.14 p = 0.69), DME (HR = 1.06, 95%CI: 0.95-1.1.9, p = 0.31), or PDR (HR = 0.81, 95%CI: 0.58-1.12, p = 0.20). CONCLUSION: We found no difference in the risk for vision-threatening diabetic retinopathy, nor for its component diseases, DME or PDR, with GLP-1RA use compared to other oral anti-hyperglycemic agents in patients with NPDR.
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We report on the case of a 19-year-old male with Stargardt disease (STGD1) who presented with a five-year history of progressive vision loss, accompanied by the recent onset of alternating exotropia. This patient initially sought care due to difficulties with near vision and tended to focus on distant objects when looking to the right. He was found to have a best-corrected visual acuity of 20/200 in both eyes. A comprehensive evaluation, including multimodal imaging and multifocal electroretinogram, was performed. Genetic testing confirmed the diagnosis of STGD1, identifying homozygous mutations in the ABCA4 gene. Interestingly, an additional heterozygous mutation in the WDPCP gene, typically associated with Bardet-Biedl syndrome, was also discovered. The patient's exotropia, an atypical feature in STGD1, underscores the importance of comprehensive clinical and genetic evaluation and the need for further research into the clinical significance of these findings.
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PURPOSE: To describe and clarify a possible pathogenetic origin for choroidal caverns in young healthy individuals through a topographical analysis using swept-source optical coherence tomography angiography (SS-OCTA). METHODS: A cross-sectional evaluation of 44 healthy volunteers (44 eyes), aged 20-32 years with no systemic or ocular comorbidities. The topographical analysis of choroidal caverns was performed through a 15 × 15â mm volumetric scan cube using SS-OCTA (PLEX Elite 9000). The number, topographic localization within the perifovea and midperipheral retina, as well as the density of choroidal caverns in the area with the highest number, were analyzed. Factors influencing the presence of choroidal caverns were identified using a logistic regression model. RESULTS: The overall prevalence of choroidal caverns was 18.2% in our cohort. The subjects exhibiting choroidal caverns presented a greater AXL (+1.19â mm, 95%CI: 0.09, 2.29). Areas with the highest density of caverns presented an average of 1.98 ± 1.01 caverns/mm2. On a qualitative evaluation, the area with the highest density was along the inferior vascular arcade in 6/8 (75%) eyes. The main predictor of choroidal cavern development was represented by AXL (adjusted risk ratio of 2.13, P = 0.02). CONCLUSION: Choroidal caverns in young, healthy individuals may form due to mechanical stress in predisposed eyes, where an increased lateral and anteroposterior choroidal stretching due to globe elongation can result in the formation of these cavities. Future longitudinal studies are encouraged to understand their prognostic implications.
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This study aimed to establish a complete atlas of retinal cells in lens-induced myopia (LIM) and electroacupuncture (EA) intervention by single-cell RNA sequencing (scRNA-seq) and to explore the potential mechanism of EA in improving experimental myopia progression in guinea pigs. scRNA-seq is used to assess changes in individual cellular gene levels in the retina of LIM- and EA-treated guinea pigs. In addition, the role of EA in slowing myopia progression by improving retinal mitochondrial function is further investigated. scRNA-seq identified ten cell clusters in the retina of LIM and EA guinea pigs and mitochondrial respiratory chain-related genes in Cones and Muller-glia cells-Cytochrome oxidase subunit III (COX3), NADH dehydrogenase subunit 4 (ND4), and NADH dehydrogenase subunit 2 (ND2) are closely related to lens-induced myopia. A comprehensive atlas in the retina of LIM and EA guinea pigs at a single-cell level is established, and the positive role of EA in improving retinal mitochondrial function to slow the experimental myopia progression in guinea pigs is revealed.