Search Results (872)

Background and Objectives: Myopia is a rapidly growing global health burden driven primarily by axial elongation, which exerts mechanical stress on the inner retina, leading to progressive thinning of the retinal nerve fiber layer (RNFL) and the ganglion cell complex (GCC). The sector-specific pattern of these changes across the full spectrum of myopia remains incompletely characterized. This study aimed to provide a comprehensive, sector-level analysis of RNFL and GCC changes across four myopia severity grades using optical coherence tomography angiography (OCTA), and to quantify their correlations with axial length (AL) and central foveal thickness (CFD). Materials and Methods: A total of 260 eyes of 130 participants were enrolled in a prospective cross-sectional study. Eyes were classified into four groups: emmetropia (EM, n = 74), low myopia (LM, n = 68), moderate myopia (MM, n = 64), and high myopia (HM, n = 54). All participants underwent cycloplegic refraction, AL measurement, and RTVue XR Avanti OCTA imaging. RNFL thickness was assessed across five peripapillary sectors, and GCC thickness across twelve macular zones. Between-group differences were analyzed using one-way ANOVA with Bonferroni post hoc correction or Kruskal–Wallis/Dunn-Bonferroni tests. Pearson correlations were used to assess associations among structural parameters, AL, and CFD. Results: Both the RNFL and GCC showed progressive, statistically significant thinning with increasing myopia severity. The superior RNFL was the only peripapillary sector that differentiated EM from LM (p = 0.039), with total thinning of 18.8 μm from EM to HM. The paratemporal GCC zone showed the earliest macular structural signal (EM vs. LM, p = 0.049). Temporal and nasal RNFL sectors showed relative preservation, with differences restricted to comparisons involving HM. AL correlated negatively with the RNFL and GCC across all sectors (r = −0.46 to −0.71), with the strongest correlation observed for the superior RNFL in HM (r = −0.71, p < 0.001). CFD demonstrated progressively stronger coupling with GCC thickness as myopia severity increased, peaking in HM (r = 0.72, p < 0.001). Conclusions: The RNFL and GCC thinning in myopia follows a progressive, sector-specific pattern driven by axial elongation. The superior RNFL and paratemporal GCC are the earliest structural indicators of inner retinal change, detectable already at the low-myopia grade. These findings support a neural-first model of myopia-related retinal remodeling and advocate for multiparametric, stage-targeted structural monitoring in clinical practice. Full article

Progranulin (PGRN) is a secreted protein composed of 7.5 granulin domains. The protein is implicated in various functions, including cell survival, inflammation, lysosomal homeostasis, tumorigenesis, and aging. Haploinsufficiency and complete loss of PGRN function cause the neurodegenerative disorders frontotemporal lobar degeneration and neuronal ceroid lipofuscinosis type 11, respectively. In the nervous system, administration of exogenous PGRN has been shown to promote the survival of various nerve cell types under different pathological conditions and to stimulate neurite outgrowth in vitro and axonal regeneration in vivo. In the retina, PGRN dysfunction results in photoreceptor and retinal ganglion cell (RGC) loss, whereas PGRN administration promotes photoreceptor cell survival. In the present study, we analyzed whether a sustained intravitreal administration of PGRN promotes the survival of axotomized RGCs and the regrowth of the lesioned axons. To this end, we generated a PGRN-overexpressing clonal neural stem cell line and injected the cells into the vitreous cavity of a mouse optic nerve crush model. The progression of the lesion-induced degeneration of RGCs was studied at different time points after the nerve crush. The regeneration of the injured RGC axons into the distal optic nerve stump was analyzed one month after nerve lesioning. We found that the intravitreally administered PGRN slowed the degeneration of the injured RGCs for up to four months, the latest post-lesion interval analyzed. Furthermore, PGRN stimulated the regeneration of some RGC axons over long distances into the distal optic nerve stumps. Taken together, our results identify PGRN as a novel neurotrophic factor for retinal ganglion cells. Full article

Glaucoma is a chronic progressive optic neuropathy and one of the leading causes of irreversible blindness worldwide. Although elevated intraocular pressure remains the most important modifiable risk factor, increasing evidence suggests that immune dysregulation and autoimmune responses also contribute substantially to disease onset and progression. Clinical studies across different glaucoma subtypes have identified subtype-dependent immune abnormalities, including altered serum autoantibody profiles, dysregulated cytokine and chemokine expression, and changes in peripheral immune cell subsets. Experimental and translational studies further indicate that multiple immunopathogenic mechanisms are involved in glaucomatous neurodegeneration, including glial cell-mediated immune responses, activation of pattern recognition receptor signalling pathways, adaptive immune responses, and complement cascade dysregulation. These processes may interact to sustain chronic neuroinflammation, promote retinal ganglion cell injury, and accelerate optic nerve degeneration. Importantly, a better understanding of immune involvement in glaucoma has generated growing interest in immunomodulatory therapy as a potential strategy beyond intraocular pressure lowering. Targeting microglial activation, inflammatory signalling pathways, adaptive immune imbalance, and complement-mediated injury has shown neuroprotective potential in animal or in vitro models, whereas clinical evidence in glaucoma patients remains limited. These findings may provide preliminary directions for future therapeutic development. In this review, we summarise the current clinical evidence linking glaucoma with autoimmunity, discuss the major immune mechanisms implicated in disease pathogenesis, and highlight recent advances in immunomodulatory therapeutic strategies. Elucidating the immune basis of glaucoma may help pave the way for more precise and effective treatments for this complex optic neuropathy. We believe that immune dysregulation in glaucoma functions as a context-dependent amplifier of retinal ganglion cell injury rather than a uniform primary driver, with innate (microglia/astrocytes), adaptive (T/B cells, HSP-specific immunity), and complement pathways interacting to sustain neuroinflammation and neurodegeneration. This integrated immune response contributes to subtype- and stage-specific vulnerability, and targeting these maladaptive immune mechanisms represents a promising, precision-guided strategy for neuroprotection beyond intraocular pressure lowering. Full article

Background and Clinical Significance: Susac syndrome is a rare autoimmune-mediated microangiopathy characterized by the triad of encephalopathy, branch retinal artery occlusion (BRAO), and sensorineural hearing loss. Due to its variable onset and protean manifestations, the syndrome is frequently misdiagnosed, potentially leading to delayed treatment and irreversible organ damage. Ocular involvement is common and often provides the first diagnostic clue. Multimodal imaging, particularly fluorescein angiography (FA) and optical coherence tomography (OCT) as well as optical coherence tomography angiography (OCT-A), enables the detection of both acute and chronic ischemic retinal changes. Their complementary application yields critical insights into disease activity, supports monitoring of relapses, and guides therapeutic strategies. Case Presentation: We describe two patients with Susac syndrome presenting with distinct ocular and neurological features. A 43-year-old male developed recurrent BRAOs in both eyes, documented by FA, OCT, and OCT-A, with preserved best-corrected visual acuity (BCVA) of 0.00 logMAR in both eyes (OU). OCT demonstrated progressive thinning of the retinal nerve fiber layer (RNFL) and inner retinal layers, consistent with sequelae of microinfarctions, while FA revealed focal arteriolar wall hyperfluorescence. Immunosuppressive therapy with corticosteroids and mycophenolate mofetil stabilized his condition. A 31-year-old female with a history of migraine and encephalopathy showed thinning of the RNFL and ganglion cell layer (GCL) with macular atrophy on OCT. FA demonstrated peripheral arteriolar wall hyperfluorescence and microaneurysms. Despite these structural alterations, visual acuity remained unaffected. Serial imaging initially demonstrated mild progression on OCT and OCT-A, followed by disease stabilization under systemic immunosuppressive therapy. Conclusions: These cases highlight the pivotal role of multimodal imaging in the early recognition and long-term monitoring of Susac syndrome. OCT provides a detailed assessment of retinal microinfarctions and chronic atrophy, while FA remains indispensable for detecting vascular leakage and disease activity. The complementary use of OCT, OCT-A, and FA enhances diagnostic accuracy, facilitates timely therapeutic interventions, and supports individualized management. Regular ophthalmological monitoring, including advanced imaging modalities, should be considered an essential component of care in Susac syndrome. Full article

Context/Objective: Fungi of the genus Tolypocladium are known for their diverse metabolic capabilities and medicinal potential. Indole diterpenoids (IDTs) represent a structurally unique class of fungal metabolites. Beyond their established roles as mycotoxins, these compounds have recently shown promise for neuroprotective effects. The objective of this study was to isolate and characterize novel IDTs from Tolypocladium album DWS131 and evaluate their neuroprotective activities and underlying mechanisms. Methods: IDTs were isolated through comprehensive chromatographic techniques. Their structures were elucidated using HRESIMS data, 1D/2D NMR spectra, and quantum chemical calculations. Neuroprotective effects were evaluated using glutamate (Glu)-induced R28 cells in vitro and N-methyl-D-aspartic acid-induced mouse models in vivo. A total of 48 mice were utilized for in vivo evaluations, divided into two separate experimental cohorts. In each cohort, mice were randomly assigned to four groups (n = 6 per group). Post-intravitreal injection, retinal survival and visual function were assessed via Brn3a-stained flat-mounts, H&E staining, f-VEP, f-ERG, and OptoDrum. Mechanisms involving the SLC7A11/GPX4/ACSL4 axis were investigated by Western blotting and immunofluorescence. Results: Seven previously undescribed paxilline-type IDTs, tolypindoles A–G (1–7), and two known analogues (8–9) were identified. Compounds 8 and 9 exhibited significant neuroprotection closely associated with the attenuation of oxidative stress and the modulation of ferroptosis-related pathways in Glu-induced R28 cells. In vivo, they preserved retinal ganglion cells, maintained retinal structure, and protected visual function, with compound 8 demonstrating superior efficacy. Mechanistic investigations revealed that both compounds modulate the SLC7A11/GPX4/ACSL4 signaling axis. Conclusions: This study expands the chemical diversity of T. album DWS131. Compounds 8 and 9, characterized by isopentenyl moieties, highlight a promising therapeutic potential for retinal neurodegenerative diseases such as glaucoma. Full article

Retinal neurovascular unit (RNVU) dysfunction underlies major blinding and neurodegenerative conditions including glaucoma, diabetic retinopathy (DR), age-related macular degeneration (AMD), retinal ischemia–reperfusion (RIR) injury, and Alzheimer’s disease (AD)-associated retinopathy. Within the RNVU, calcium ions coordinate neurotransmission, glial activation, vascular tone, and blood–retinal barrier maintenance, and calcium dysregulation is emerging as a unifying pathogenic hub across these conditions. Although upstream triggers differ, including mechanical stress in glaucoma, hyperglycemia in DR, oxidative damage in AMD, ischemic energy failure in RIR, and amyloid-β–driven endoplasmic reticulum stress in AD, all converge on disruption of intracellular calcium homeostasis, producing shared downstream consequences including excitotoxic injury of retinal ganglion cells (RGCs), Müller cell reactive gliosis, and pericyte hypercontraction. Broad-spectrum calcium channel blockade has shown limited clinical success, underscoring the need for cell-type-specific and pathway-selective approaches. This review therefore catalogs key interventional nodes, including transient receptor potential (TRP) channel antagonists, T-type calcium channel inhibitors, calcium/calmodulin-dependent protein kinase II (CaMKII) suppressors, and mitochondrial permeability transition pore (mPTP) inhibitors, and discusses how precision targeting of these pathways may restore RNVU homeostasis and open a therapeutic window into central nervous system (CNS) degenerative disorders. Full article

Glaucoma is a collection of disorders that result in permanent vision loss and is characterized by a gradual decline in retinal ganglion cells. While it may not always be high, intraocular pressure (IOP) is the sole risk factor that can be modified according to extensive clinical research. Glaucoma remains the leading cause of irreversible blindness, yet early treatment lowering intraocular pressure is effective in slowing the rate of visual deterioration. Issues like poor absorption, low bioavailability, and short drug resistance time have thus made the management of glaucoma challenging when using conventional ophthalmic drugs. Thus, extensive research has been conducted to explore specific nanodrug delivery systems from various nanocarriers such as nanoparticles, micelles, liposomes and nanofibers, with a focus on systems that have achieved drug release for more than 12 h. These carriers have demonstrated substantial improvements in a lot of the evaluated aspects: enhancing ocular barrier-crossing capabilities, improving bioavailability, prolonging drug release, targeting active tissues of interest, and reducing IOP. This review covers recent developments in nanocarrier ocular delivery systems regarding the management of glaucoma. In this study, the advantages and disadvantages of each system were evaluated and their potential for advancing translation from research to clinic were assessed. Full article

Background/Objectives: Using a well-established model of streptozotocin-induced diabetic retinopathy (DR), this study sought to evaluate the neuroprotective effect of intravitreal Forskolin (FSK) on retinal ganglion cell survival and glial activation and explore the association of circulating miR-200b with metabolic and oxidative stress in DR. Methods: A total of 18 male Wistar rats were divided into a control group (n = 6) and a streptozotocin-induced diabetic group (n = 12), which were further divided into diabetic control and FSK-treated groups (n = 6 each). Total antioxidant capacity (TAC), total peroxide (TP), triglycerides (TGs), total cholesterol, and high-density lipoprotein cholesterol (HDL-C) were measured. qRT-PCR analysis for miRNA-200b and immunohistochemistry were performed. Results: Diabetic rats showed oxidative stress and hyperlipidemia associated with increased circulating miR-200b levels. The retina showed reduced neuron numbers (Caspase-3), altered glial and astrocyte staining (IBA1, GFAP), and changes in microglia/macrophage morphology and distribution. Intravitreal FSK improved retinal ganglion cell survival and reduced glial activation, while systemic lipid profile and oxidative stress markers remained largely unchanged. Circulating miR-200b levels showed a positive correlation with oxidative stress markers across groups. Conclusions: Intravitreal FSK was able to limit the disease exacerbation via improved neuronal survival through inhibition of apoptosis. FSK did not produce observable qualitative changes in GFAP expression or IBA1+ cell morphology under the conditions tested. Full article

Glaucoma remains a primary cause of blindness, yet its pathogenesis often extends beyond intraocular pressure (IOP). This review integrates four converging lines of metabolic evidence—aqueous humor (AH) metabolomics, kynurenine pathway (KP) activity, tetrahydrobiopterin (H4BIP) biology, and NAD/one-carbon dysfunction—into a testable framework for retinal ganglion cell vulnerability. By utilizing a systematic AH metabolomics atlas covering glaucoma, pseudoexfoliation, and diabetes on a standardized HILIC-LC-HRMS platform, we demonstrate that, while aromatic amino acid elevations are non-specific markers, kynurenine monooxygenase (KMO) upregulation is a condition-specific glaucoma signature. These local findings are corroborated by systemic evidence: POAG patients exhibit significant folic acid deficiency (p = 0.007) and elevated alpha-1-antitrypsin (AAT). Critically, AAT correlates inversely with both serum folate (r_s = −0.485, p < 0.001) and retinal nerve fiber layer thickness (r_s = −0.386, p = 0.017), providing the first in-patient evidence linking systemic inflammation to structural optic nerve damage. We conclude that KMO serves as a critical enzymatic node linking tryptophan metabolism, H4BIP availability, and NAD synthesis. These results characterize glaucoma as a disease of progressive cofactor failure and define a research agenda for multimodal metabolic neuroprotection. Full article

Background and Objectives: Open-angle glaucoma subtypes share a structural phenotype but differ in pathophysiology: pseudoexfoliative glaucoma (PXG) involves vascular endothelial dysfunction associated with deposition of exfoliative material, whereas normal-tension glaucoma (NTG) reflects primary vascular dysregulation in the absence of elevated intraocular pressure. We characterized subtype-specific OCT angiography (OCTA) profiles obtained from a 3 × 3 mm macular scan and evaluated their discriminatory power for pairwise subtype classification. Materials and Methods: This was a single-center, cross-sectional study of 304 eyes: 198 glaucomatous eyes—primary open-angle glaucoma (POAG, glaucoma simplex in our clinical nomenclature), n = 102; PXG (glaucoma capsulare), n = 68; NTG (glaucoma sine tensio), n = 28—and 106 healthy controls. The Cirrus HD-OCT 5000 AngioPlex 3 × 3 mm OCTA protocol was used to assess vessel density (VD), perfusion density, foveal avascular zone (FAZ) morphology, ganglion cell complex (GCC), and retinal nerve fiber layer (RNFL) thickness. Analyses included Kruskal–Wallis tests with Bonferroni post hoc correction, ROC analysis with DeLong comparison of combined versus structural-only models, multivariate regression, and an exploratory XGBoost classifier with SHAP-based interpretation. Results: VD Inner and Perfusion Inner were lower in PXG (16.37 ± 3.33%; 0.31 ± 0.05) than in POAG (18.73 ± 3.41%; 0.34 ± 0.05; both p < 0.001); Perfusion Inner was also lower than in NTG (p < 0.05). FAZ Area was largest in NTG (0.27 ± 0.11 mm²) and greater than in PXG (0.19 ± 0.08; p < 0.01); FAZ Circularity differed across subtypes (p < 0.001). Combined OCTA–structural models outperformed structural-only models for POAG vs. PXG (DeLong p = 0.002) and for PXG vs. NTG (AUC = 0.770; p = 0.010). Sector-resolved Spearman analysis revealed subtype-specific coupling: in NTG, VD Inner and Perfusion Inner correlated with the inferior RNFL (r = 0.53 and r = 0.52; both p < 0.01); in PXG, coupling shifted nasally (r = 0.41 and r = 0.46; both p < 0.001). The exploratory XGBoost classifier separated glaucoma from controls with an internal cross-validated AUC of 0.975 ± 0.008 (5-fold CV; not externally validated); FAZ Circularity (mean |SHAP| = 0.418) and FAZ Area (0.411) were the top inter-subtype features, supported by case-level SHAP. RNFL avg and average GCC independently predicted MD across subtypes; in PXG, Perfusion Inner also predicted MD (β = −32.78; p = 0.032). Conclusions: In this single-center, cross-sectional cohort, OCTA revealed subtype-associated macular microvascular profiles that are complementary to structural OCT. Reduced vessel and perfusion density characterized PXG, whereas FAZ enlargement and reduced circularity distinguished NTG and PXG. Vascular–structural coupling was nasal-predominant in PXG and inferior-predominant in NTG. Combined multimodal models outperformed structural-only approaches. Macular perfusion additionally predicted MD in PXG. The XGBoost/SHAP analysis is exploratory; prospective and externally validated studies are required before clinical deployment. Full article

Background: The photopic negative response (PhNR) of the full-field electroretinogram is a retinal ganglion cell-weighted functional signal increasingly proposed as a clinical biomarker. Despite extensive study across ocular and systemic diseases, its precise clinical role and incremental value remain incompletely established. Methods: This narrative review synthesizes key human studies of the photopic negative response, with emphasis on physiological basis, recording methodology, and clinical contexts in which PhNR may provide added functional insight. Results: In glaucoma, PhNR provides an objective measure of retinal ganglion cell dysfunction that correlates moderately with optical coherence tomography (OCT)-derived structural loss and visual field indices, but with substantial inter-individual variability. Its greatest clinical utility lies in early disease detection, cross-sectional functional assessment, and documenting short-term functional changes following intraocular pressure reduction, rather than longitudinal progression monitoring. Beyond glaucoma, PhNR reveals inner retinal dysfunction in systemic and genetic conditions, particularly idiopathic intracranial hypertension and diabetes, where retinal ganglion cells may reflect broader neurological or metabolic stress. Conclusions: PhNR is best viewed not as a standalone diagnostic or progression tool, but as a complementary functional biomarker that adds objective insight when structural imaging or psychophysical testing is limited or discordant. Its role aligns closely with the retina’s emerging function as a mirror of systemic and genetic disease, provided recordings are standardized and results interpreted cautiously. Full article

Visual prostheses aim to approximate biomimetic visual function by electrically simulating surviving retinal neurons. Improving the spatial resolution of electrically elicited artificial vision remains a critical challenge for retinal prostheses. We investigate how dynamic virtual channel (DVC) parameters shape retinal ganglion cell (RGC) population responses to improve spatial precision and activation efficiency in epiretinal stimulation. We developed a computational modeling framework to quantify DVC performance using a hierarchical optimization strategy. First, static virtual channels (SVCs) were used to map how current ratio (α) and stimulus intensity govern RGC activation, defining an optimal SVC parameter space. Building on this baseline, DVC protocols were refined by evaluating the combined effects of inter-virtual–channel interval (ΔT), α, and intensity. This strategy significantly reduces the complexity of DVC parameter optimization. Under SVC stimulation, increasing intensity improved the linearity of receptive field (RF) centroid displacement with α, while α and intensity jointly set RF centroid location and activated area. Under DVC stimulation, ΔT strongly modulated RGC activation, especially at short intervals. Initializing from SVC-optimized parameters, tuning ΔT and intensity produced more confined activation at lower stimulus intensities than SVC, indicating that DVC can serve as a novel stimulation strategy to enhance spatial precision and activation efficiency in retinal stimulation. This study provides the first systematic analysis of retinal DVC stimulation and a practical optimization framework for next-generation prostheses. Full article

Alzheimer’s disease (AD) is increasingly recognized as a multisystem neurodegenerative disorder in which sensory dysfunction accompanies cognitive decline. As an accessible extension of the central nervous system, the retina provides a valuable window for investigating early neurodegenerative processes; however, the cellular mechanisms underlying AD-associated retinal pathology remain incompletely understood. Here, using the APP/PS1 mouse model, we systematically examined structural, functional, and glial alterations in the retina across disease stages. Despite robust age-dependent amyloid plaque accumulation in visual-related brain regions, no plaque-like β-amyloid (Aβ) deposits were detected in the retina even at advanced ages. Nevertheless, young APP/PS1 mice exhibited early thinning of inner retinal layers, impaired retinal electrophysiological responses, and reduced excitatory synaptic inputs to retinal ganglion cells (RGCs), preceding overt neuronal loss. These neuronal changes were accompanied by pronounced Müller glial activation, characterized by upregulation of gliosis markers and extensive morphological remodeling. Functional analyses further revealed dynamic alterations in glial homeostasis, including early elevation followed by age-dependent decline of glutamine synthetase activity, together with increased expression and disrupted perivascular polarity of aquaporin-4. Consistently, transcriptomic profiling of young AD retinas identified coordinated dysregulation of genes involved in amino acid metabolism, transport, and oxidative stress responses. Together, our findings identify Müller glial remodeling as an early feature of AD-associated retinal pathology that coincides with synaptic vulnerability of RGCs and occurs independently of local Aβ plaque deposition, highlighting retinal glia as potential early indicators and modulators of neurodegeneration. Full article

Retinal ganglion cell (RGC) degeneration underlies glaucomatous optic neuropathy and remains a leading cause of irreversible vision loss worldwide. Although elevated intraocular pressure (IOP) is the primary modifiable risk factor, RGC death reflects converging mechanisms including mechanical stress, vascular insufficiency, metabolic dysfunction, and neuroinflammation. We conducted a PRISMA-guided systematic review with PICOS-defined eligibility criteria, searching PubMed, Cochrane Library, ScienceDirect, Scopus, Google Scholar, and ProQuest for studies through January 2026 on RGC degeneration and neuroprotective or regenerative therapies in glaucoma. Included studies supported OCT-based structural assessment and imaging biomarkers as essential tools for early detection, risk stratification, and monitoring of progression and treatment response. Continued RGC loss despite IOP control in many patients highlights the need for mechanism-based interventions; neuroprotective strategies targeting excitotoxicity, oxidative stress, mitochondrial dysfunction, and neurotrophic insufficiency are emerging, while stem cell and gene-based regenerative therapies remain under active investigation. Integrating molecular insights with advanced imaging and biomarker-guided endpoints may enable earlier, more individualized intervention and help explain progression despite adequate pressure control. Full article