Search Results (360)

Retinal degeneration is associated with dietary factors and environmental light exposure. This study investigated the effects of a high-fructose high-fat (HFHF) diet on susceptibility to blue light (BL)-induced retinal damage. Male ICR mice were randomized into three groups: control, BL alone, and BL plus HFHF diet (BL + HFHF). The BL + HFHF group consumed the HFHF diet for 40 weeks, followed by 8 weeks of low-intensity BL exposure (465 nm, 37.7 lux, 0.8 μW/cm²) for 6 h daily. The BL group underwent the same BL exposure while kept on a standard diet. Histopathological analysis showed that, under BL exposure, the HFHF diet significantly reduced the number of photoreceptor nuclei and the thickness of the outer nuclear layer and inner/outer segments compared to the BL group (p < 0.05). While BL exposure alone caused oxidative DNA damage, rhodopsin loss, and Müller cell activation, the combination with an HFHF diet significantly amplified the oxidative DNA damage and Müller cell activation. Moreover, the HFHF diet increased blood–retinal barrier permeability and triggered apoptosis under BL exposure. Mechanistically, the BL + HFHF group exhibited increased retinal advanced glycated end product (AGE) deposition, accompanied by the activation of the receptor for AGE (RAGE), NFκB, and the NLRP3 inflammasome-dependent IL-1β pathway. In conclusion, this study underscores that unhealthy dietary factors, particularly those high in fructose and fat, may intensify the hazard of BL and adversely impact visual health. Full article

Non-arteritic anterior ischemic optic neuropathy (NAION) leads to retinal ganglion cell (RGC) loss and visual impairment, with no effective treatment. This study investigated the neuroprotective effect of 670 nm photobiomodulation (PBM) in a rat NAION model (rNAION). Wistar rats received 670 nm light exposure (10-min, 3000 lux) twice daily for 3 days after rAION injury, followed by 4 days of light treatment once a day. This study evaluated the neuroprotective effects of 670 nm light in an rNAION model. Rats received 670 nm light therapy (10 min/day, 3000 lux) for seven days post-injury. Treatment improved visual function (a 3.36-fold increase in FVEP amplitude), enhanced RGC survival (1.55-fold), and reduced apoptosis (a 15.86-fold reduction in TUNEL-positive cells). Inflammatory cytokines and ED1+ macrophage infiltration were significantly decreased. Oxidative stress was attenuated, with increased ATP, Nrf2, and PGC-1α levels and improved mitochondrial dynamics. These findings support 670 nm light as a potential therapy for NAION. Full article

Background: The retina, a light-sensitive tissue of the central nervous system that is located at the posterior part of the eye, is particularly vulnerable to alterations in oxygen levels. In various retinal diseases, such as central retinal vein occlusion, glaucoma, and diabetic retinopathy, hypoxia (a condition of low oxygen levels) is commonly observed. Müller glia, the principal glial cells in the retina, play a crucial role in supporting the metabolic needs of retinal neurons. They are also responsible for sensing oxygen levels and, in response to hypoxia, express Hypoxia-Inducible Factor 1 (HIF-1), a transcription factor that activates signaling pathways related to hypoxia. Methods: In this study, primary rat Müller glial cells were cultured and exposed to a 1% oxygen for 72 h. Following this, immunohistochemical assays were conducted to assess the effects of hypoxia on various parameters, including HIF-1α expression, cell survival, Müller glia-specific markers (CRALBP and GS), gliosis (GFAP expression), apoptosis (caspase-3 expression), cell proliferation (Ki-67 expression), and metabolic stress (indicated by the number of mitochondria per cell). Results: Under hypoxic conditions, a decrease in Müller glial survival and proliferation was observed. Conversely, there was an increase in HIF-1α expression, GFAP expression, caspase-3-positive cells, and the number of mitochondria per cell. However, no significant changes were noted in the expression of the Müller glial markers GS and CRALBP. Conclusions: In conclusion, hypoxia resulted in reduced proliferation and survival of Müller glial cells, primarily due to increased apoptosis and heightened metabolic stress. Full article

Background: An acute angle-closure attack (AAC) is an ocular emergency that results from a rapid increase in intraocular pressure (IOP). Sustained IOP elevation induces severe degeneration of retinal ganglion cells (RGCs) without treatment. Overactivated microglia, key participants in innate immune responses, have critical roles in the pathogenesis of IOP-induced RGC death, although precise mechanisms remain unclear. In the present study, we used a rat ex vivo acute glaucoma model to investigate the role of microglial signaling in RGC death and examined whether pharmacological depletion of microglia using a CSF-1R inhibitor, PLX5622, exerts neuroprotection against pressure-induced retinal injury. Methods: Ex vivo rat retinas were exposed to hydrostatic pressure (10 mmHg or 75 mmHg) for 24 h. Pressure-dependent changes in retinal microglia and RGCs were detected by immunofluorescence. Morphological changes in the retina and RGC apoptosis were examined using light microscopy and TUNEL staining, respectively. The expression of NLRP3, active caspase-1, pro IL-1β, and IL-1β were examined using Western blotting. Effects of PLX5622, an agent that depletes microglia, were examined in morphology, apoptosis, and protein expression assays, while TAK-242, a TLR4 inhibitor, was examined against protein expression. Results: Pressure loading at 75 mmHg markedly increased activated microglia and apoptotic RGCs in the isolated retinas. Western blotting revealed increases in expression of NLRP3, active caspase-1, pro IL-1β, and IL-1β at 75 mmHg compared to 10 mmHg. Inhibition of pressure-induced increases in NLRP3 by TAK-242 indicates that pressure elevation induces RGC death via activation of the TLR4–NLRP3 inflammasome cascade. PLX5622 depleted microglia at 75 mmHg and significantly decreased expression of NLRP3, active caspase-1, pro IL-1β, and IL-1β at 75 mmHg, resulting in preservation of RGCs. Conclusions: These results indicate that pressure elevation induces proliferation of inflammatory microglia and promotes IL-1β production via activation of the TLR4–NLRP3 inflammasome cascade, resulting in RGC death. Pharmacological depletion of microglia with PLX5622 could be a potential neuroprotective approach to preserve RGCs from inflammatory cytokines in AAC eyes. Full article

Retinal detachment (RD) is a serious clinical condition that significantly impacts patients’ quality of life. Its management involves considering several clinical factors that may affect the therapeutic approach. Inflammatory complications can affect visual recovery, long-term outcomes, and prognosis. Understanding the underlying inflammatory mechanisms is key to improving personalized medicine and optimizing therapeutic approaches to management. This review comprehensively searched scientific databases (Medline, Web of Science, and Scopus), considering clinical and experimental studies published between 1999 and 2025. Specific MeSH terms and predefined inclusion and exclusion criteria were used to select the most relevant papers. A total of 140 studies were analyzed. The findings were analyzed qualitatively and illustrated with images from clinical practice. Several studies have demonstrated the critical role of cytokines in retinal inflammation, highlighting their importance in regulating the immune response following RD. In addition, oxidative stress, apoptotic mechanisms, and glia activation, particularly Müller cells and microglia, have been identified as crucial elements in the progression of retinal damage. In this sense, inflammation poses significant clinical challenges that require more effective therapeutic strategies. In conclusion, this review differs from previous literature by emphasizing the translational implications of inflammatory mechanisms in RD and by comparing experimental and clinical data. The management of RD should consider not only surgical aspects, but also modulation of the inflammatory response to improve visual outcomes and prevent long-term complications. Full article

Wipe-out is defined as a sudden, unexplained, and irreversible loss of residual central vision following glaucoma surgery, typically in eyes with advanced visual field damage and severely compromised optic nerves. The purpose of this review is to critically assess the current incidence, risk factors, pathophysiological mechanisms, and clinical relevance of “wipe-out”, a rare but devastating complication of glaucoma surgery characterized by sudden, unexplained central vision loss postoperatively. A comprehensive literature review was conducted, analyzing key peer-reviewed studies from electronic databases (PubMed, Medline, and Google Scholar) published up to 2025. The data from the literature published prior to the year 2000 suggest that wipe-out incidences range broadly from <1% to 13%. Contemporary prospective studies and large-scale reviews indicate a significantly lower current incidence, frequently below 1%. Identified risk factors include severe preoperative visual field loss (especially split fixation), older age, immediate postoperative hypotony, and compromised optic nerve head perfusion. The proposed mechanisms involve acute vascular insults, ischemia–reperfusion injury, and accelerated apoptosis of already vulnerable retinal ganglion cells. Modern MIGS and refined trabeculectomy techniques exhibit notably lower wipe-out risks compared to historical data. The literature emphasizes preventive management, including careful patient selection, incremental intraocular pressure reduction, and minimally invasive anesthetic approaches. Although wipe-out syndrome represents a serious complication, its incidence in modern glaucoma surgery is minimal. The considerable benefits of contemporary surgical approaches—particularly MIGS—in preserving vision clearly outweigh this very low risk. Ophthalmologists should remain vigilant but confident in the safety and efficacy of modern glaucoma surgical techniques, emphasizing proactive intervention to prevent blindness rather than avoiding necessary surgery in consideration of the minimal risk of wipe-out. Full article

Hyperglycemia is a key factor in diabetic retinopathy which leads to blindness. O-linked-N-acetylglucosamine (O-GlcNAc) modification changes are linked to various diseases, including diabetic retinopathy. This research aims to study the roles of Txnip and Trx in influencing O-GlcNAc in photoreceptor cells during diabetic retinopathy. A diabetic mouse model and 661w cells, after exposure to high glucose, were employed as models. H&E staining and ERG were used to evaluate the morphology and function of the retina, respectively. Western blotting was used to analyze protein expression, a TUNEL assay was used to measure apoptosis, and a co-immunoprecipitation (CO-IP) assay was used to detect the interactions of protein. In diabetic mice, electroretinogram (ERG) amplitude wave, retinal thickness, and body weight decreased. Glial fibrillary acidic protein (GFAP), Iba1 expression, and blood glucose level increased. In vitro, the percentage of apoptotic cell, Bax, and caspase3 levels increased, and Bcl2 decreased in 661w cells under high-glucose conditions. Moreover, Txnip expression was upregulated, while Trx was downregulated. Additionally, a Western blot analysis revealed that high-glucose exposure led to increased O-GlcNAc modification both in vivo and in vitro. The CO-IP results show that Txnip interacted with O-GlcNAc modifications. S-opsin expression was significantly downregulated in vitro under high-glucose conditions. Knockdown Txnip or upregulation Trx could reverse or delay apoptosis in 661w cells under hyperglycemic conditions. Txnip/Trx is a potential element in regulating photoreceptor apoptosis in diabetic retinopathy. The underlying mechanism is linked to regulation of O-GlcNAc modification in photoreceptor cells in DR. Full article

Background/Objectives: Age-related macular degeneration (AMD) is the third leading cause of irreversible blindness in elderly individuals aged over 50 years old. Oxidative stress plays a crucial role in the etiopathogenesis of multifactorial AMD disease. The phospholipid bilayer EVs derived from the culture-conditioned medium of human induced pluripotent stem cell (hiPSC) differentiated retinal organoids aid in cell-to-cell communication, signaling, and extracellular matrix remodeling. The goal of the current study is to establish and evaluate the encapsulation of a hydrophobic compound, cannabidiol (CBD), into retinal organoid-derived extracellular vesicles (EVs) for potential therapeutic use in AMD. Methods: hiPSC-derived retinal organoid EVs were encapsulated with CBD via sonication (CBD-EVs), and structural features were elucidated using atomic force microscopy, nanoparticle tracking analysis, and small/microRNA (miRNA) sequencing. ARPE-19 cells and oxidative-stressed (H₂O₂) ARPE-19 cells treated with CBD-EVs were assessed for cytotoxicity, apoptosis (MTT assay), reactive oxygen species (DCFDA), and antioxidant proteins (immunohistochemistry and Western blot). Results: Distinct miRNA cargo were identified in early and late retinal organoid-derived EVs, implicating their roles in retinal development, differentiation, and functionality. The therapeutic effects of CBD-loaded EVs on oxidative-stressed ARPE-19 cells showed greater viability, decreased ROS production, downregulated expression of inflammation- and apoptosis-related proteins, and upregulated expression of antioxidants by Western blot and immunocytochemistry. Conclusions: miRNAs are both prognostic and predictive biomarkers and can be a target for developing therapy since they regulate RPE physiology and diseases. Our findings indicate that CBD-EVs could potentially alleviate the course of AMD by activating the targeted proteins linked to the adenosine monophosphate kinase (AMPK) pathway. Implicating the use of CBD-EVs represents a novel frontline to promote long-term abstinence from drugs and pharmacotherapy development in treating AMD. Full article

Age-related retinopathy is one of the leading causes of visual impairment and irreversible blindness, characterized by progressive neuronal and myelin loss. The damages caused by oxidation contributes to the hallmarks of aging and represents fundamental components in pathological pathways that are thought to drive multiple age-related retinopathies. Quercetin (Que), a natural polyphenol abundant in vegetables, herbs, and fruits, has been extensively studied for its long-term antioxidative effects mediated through diverse mechanisms. Additionally, Que and its derivatives exhibit a broad spectrum of pharmacological characteristics in the cellular responses of age-related retinopathy induced by oxidative stress, including anti-inflammatory, anti-neovascularization, regulatory, and neuroprotective effects in autophagy and apoptosis processes. This review mainly focuses on the antioxidative mechanisms and curative effects of Que treatment for various age-related retinopathies, such as retinitis pigmentosa, diabetic retinopathy, age-related macular degeneration, and glaucoma. Furthermore, we discuss emerging technologies and methods involving Que and its derivatives in the therapeutic strategies for age-related retinopathies, highlighting their promise for clinical translation. Full article

Neuronal ceroid lipofuscinoses (NCLs) are a group of autosomal recessive neurogenetic disorders caused by mutations in 14 different genes. CLN6 disease manifests as variant late-infantile NCL (vLINCL) or as an adult variant. In childhood, symptoms include speech delay, vision loss, cognitive and motor decline, seizures, and early death. An in-depth characterization of a naturally occurring Cln6 mutant mouse (Cln6^nclf) is presented, with implications for translational research. The expanded phenotype provides data showing early death, vision loss, and motor deficits in male and female Cln6^nclf mice. Diminished visual acuity in Cln6^nclf mice was noted at 28 weeks of age, but the pathological loss of retinal layers began as early as 2 weeks or postnatal day 14 (P14). Apoptosis was confirmed by TUNEL staining in the Cln6^nclf mouse brain at P8 and in the retina at P12. A peak in glial fibrillary acidic protein (GFAP) expression was established as a normal developmental phenomenon in the wild-type and Cln6^nclf mouse brain cerebellum and the CA2–CA3 regions of the hippocampus at P8. In Cln6^nclf mice, GFAP levels were elevated at P12 in the cerebellum and hippocampus. In the retina, a developmental peak in gliosis was absent, with increased astrogliosis noted at P6 and P8 in female and male Cln6^nclf mice, respectively. This highlights the lack of a sex-dependent response in wild-type mice. These novel data position the Cln6^nclf mouse model as a useful tool for screening potential therapeutics for human CLN6 disease. Full article

Purpose: The aim of this study was to investigate the protective effects of systemically administered tauroursodeoxycholic acid (TUDCA) in an optic nerve crush (ONC) mouse model of retinal ganglion cell (RGC) death. Methods: C57BL/6J mice were injected intraperitoneally (i.p.) three times per week with TUDCA (500 mg/kg) for two weeks, after which unilateral ONC was performed. A control cohort was identically treated with a drug vehicle (phosphate buffered saline; PBS). A separate cohort did not undergo any injections or surgeries (this was termed the “Naïve” group). Pattern electroretinography (PERG) was recorded 3 days after ONC. Retinas were harvested for whole-mount immunofluorescence staining with an antibody against RGC marker Brn3a and imaged by fluorescent confocal microscopy. Apoptotic cells in the ganglion cell layer (GCL) were detected by Terminal Deoxynucleotidyl Transferase-Mediated dUTP Nick End Labeling (TUNEL) performed on fixed retina sections. Glial fibrillary acidic protein (GFAP) immunostaining on fixed retina sections was conducted to detect the activation of Müller cells. Total RNA was extracted from retinas and expression of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and IL-10 was determined by digital droplet PCR (ddPCR). Results: TUDCA treatment preserved visual function as assessed by PERG. P1 and N2 amplitudes from the PBS-treated ONC group were significantly diminished compared to those of the Naïve group (p < 0.001). TUDCA treatment prevented this diminution. The amplitudes of P1 and N2 in the TUDCA-treated ONC group were statistically indistinguishable from those of the Naïve group and were higher than the PBS-treated ONC group (TUDCA+ONC vs. PBS+ONC, P1: 6.99 ± 0.89 µV vs. 3.60 ± 0.69 µV, p < 0.01; N2: −9.30 (IQR: −13.43–−6.44) µV vs. −4.47 (IQR: −10.26–−2.17) µV). TUDCA treatment preserved RGCs. The ONC-vehicle-only group had 25% fewer RGCs (Brn3a-positive cells) than Naïve eyes (p < 0.0001). TUDCA treatment nearly completely prevented this loss, preserving all but 7.7% of the RGCs, and the number of RGCs in the TUDCA-treated ONC group was significantly higher than in the PBS-treated ONC group (TUDCA+ONC vs. PBS+ONC, 1738.00 ± 14.43 cells per field vs. 1454.00 ± 6.55 cells per field, p < 0.0001). The number of TUNEL-positive cells in the GCL (Naïve vs. PBS+ONC group: 1.00 (IQR: 0.00–2.00) % vs. 37.00 (IQR: 8.50–48.50) %, p < 0.05) and GFAP-positive fibers transversing retina sections (Naïve vs. PBS+ONC group: 33.00 ± 1.15 vs. 185.70 ± 42.37 fibers/retina, p < 0.05), and the expression of IL-6, TNF-α were significantly greater in the PBS-treated ONC group compared to that of the Naïve group (Naïve vs. PBS+ONC group, IL-6: 0.07 (IQR: 0.06–0.31) vs. 0.99 (IQR: 0.56–1.47), p < 0.05, TNF-α: 0.19 ± 0.069 vs. 1.39 ± 0.23; p < 0.01), an increase not observed with TUDCA treatment. Conclusions: Systemic TUDCA treatment significantly preserved RGC function and survival in the mouse ONC model of RGC damage. TUDCA treatment prevented RGC apoptosis, Müller glial cell activation, and retinal expression of several inflammatory cytokines. These data suggest that TUDCA is a promising therapeutic candidate for preserving RGC numbers and function. Full article

The disruption of microglial homeostasis and cytokine release are critical for neuroinflammation post-injury and strongly implicated in retinal neurodegenerative diseases like glaucoma. This study examines microglial responses to chemical hypoxia induced by cobalt chloride (CoCl₂) in BV-2 murine microglial cells, focusing on signaling pathways and proteomic alterations. We assessed the protective effects of monoclonal antibodies against TNFα and IL-1β. CoCl₂ exposure led to decreased cell viability, reduced mitochondrial membrane potential, increased lactate dehydrogenase release, elevated reactive oxygen species generation, and activation of inflammatory pathways, including nitric oxide synthase (iNOS), STAT1, and NF-κB/NLRP3. These responses were significantly mitigated by treatment with anti-TNFα and anti-IL-1β, suggesting their dual role in reducing microglial damage and inhibiting inflammatory reactivity. Additionally, these treatments reduced apoptosis by modulating ATF4 and the p38 MAPK/caspase-3 pathways. Label-free quantitative mass spectrometry-based proteomics and Gene Ontology revealed that CoCl₂ exposure led to the upregulation of proteins primarily involved in endoplasmic reticulum and catabolic processes, while downregulated proteins are associated with biosynthesis. Anti-TNFα and anti-IL-1β treatments partially restored the proteomic profile toward normalcy, with network analysis identifying heat shock protein family A member 8 (HSPA8) as a central mediator in recovery. These findings offer insights into the pathogenesis of hypoxic microglial impairment and suggest potential therapeutic targets. Full article

Background/Objectives: This study aimed to investigate the efficacy of topical dopamine administration in inhibiting form deprivation (FD) myopia in a rabbit model. Methods: A total of 16 neonatal New Zealand white rabbits were randomly assigned to two groups: a control group and a dopamine treatment group. FD myopia was induced in both groups by applying a light diffuser to one eye. The dopamine group received daily topical instillations of 4% dopamine in the eye with FD myopia, while the control group received normal saline instillations over a four-week period. Axial length measurements were taken to assess the degree of myopia, and histological analysis was performed to evaluate retinal safety and structural integrity. Results: The results indicated that dopamine treatment significantly inhibited axial elongation of the FD eyes compared to the control group, with measurements of 15.07 ± 0.34 mm for the dopamine group versus 15.63 ± 0.33 mm for the control group (p = 0.015). Histological analysis showed no evidence of structural alterations or apoptosis in the retina, confirming the safety of topical dopamine. Conclusions: Topical dopamine appears to be a promising therapeutic approach for controlling the progression of myopia in a rabbit model, demonstrating significant efficacy in reducing axial elongation without inducing ocular toxicity. These findings highlight the potential of dopamine in managing myopia and warrant further investigation in clinical settings. Full article

The role of the mitogen-activated protein kinase (MAPK) pathway in choroidal neovascularization (CNV) remains unclear. This study investigates the involvement of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 pathways in CNV development, as well as the therapeutic potential of sprouty 2 (SPRY2), an MAPK inhibitor, in a laser-induced mouse model. The expressions of ERK, JNK, and p38 proteins were analyzed using Western blotting and immunostaining. Immunofluorescence imaging revealed increased p-ERK and p-JNK expression in the retina, retinal pigment epithelium (RPE), and choroid up to day 7. Co-immunostaining showed p-ERK colocalized with CD31, CD11b, F4/80, cytokeratin, and GFAP in the retina, while p-JNK and p-p38 were associated with angiogenesis and inflammation throughout the retina and choroid. Compared to aflibercept, SPRY2 administration significantly inhibited CNV lesions, endothelial proliferation, fibrosis, and apoptosis, while better-preserving RPE integrity. SPRY2-treated mice showed a stronger reduction in CNV-related inflammation, epithelial–mesenchymal transition, and photoreceptor apoptosis. These results highlight the MAPK pathway’s role in CNV pathogenesis, with ERK primarily mediating Müller cell gliosis and JNK, contributing to angiogenesis and inflammation. SPRY2 effectively suppressed CNV lesions, supporting its potential as a therapeutic target for CNV treatment via MAPK pathway modulation. Full article

Background/Objectives: Activation of cannabinoid CB1 or CB2 receptors induces the death of glial progenitors from the chick retina in culture. Here, by using an enriched retinal glial cell culture, we characterized some mechanisms underlying glial death promoted by cannabinoids. Methods and Results: Retinal cultures obtained from 8-day-old (E8) chick embryos and maintained for 12–15 days (C12–15) were used. MTT assays revealed that the CB1/CB2 agonist WIN 55,212-2 (WIN) decreased cell viability in the cultures in a time-dependent manner, with a concomitant increase in extracellular LDH activity, suggesting membrane integrity loss. Cell death was also dose-dependently induced by cannabidiol (CBD), Δ⁹-tetrahydrocannabinol (THC), and CP55940, another CB1/CB2 agonist. In contrast to WIN-induced cell death that was not blocked by either antagonist, the deleterious effect of CBD was blocked by the CB2 receptor antagonist SR144528, but not by PF514273, a CB1 receptor antagonist. WIN-treated cultures showed glial cells with large vacuoles in cytoplasm that were absent in cultures incubated with WIN plus 4-phenyl-butyrate (PBA), a chemical chaperone. Since cannabinoids induced the phosphorylation of eukaryotic initiation factor 2-alfa (eIF2α), these results suggest a process of endoplasmic reticulum (ER) swelling and stress. Incubation of the cultures with WIN for 4 h induced a ~five-fold increase in the number of cells labeled with the ROS indicator CM-H2DCFDA. WIN induced the phosphorylation of JNK but not of p38 in the cultures, and also induced an increase in the number of glial cells expressing cleaved-caspase 3 (c-CASP3). The decrease in cell viability and the expression of c-CASP3 was blocked by salubrinal, an inhibitor of eIF2α dephosphorylation. Conclusions: These data suggest that cannabinoids induce the apoptosis of glial cells in culture by promoting ROS production, ER stress, JNK phosphorylation, and caspase-3 processing. The graphical abstract was created at Biorender.com. Full article