Ginkgo Biloba Standardized Extract EGb 761 Reduces Light and Toxin-Induced Photoreceptor Cell Damage via Regulating Oxidative Stress and Autophagy.

Quercetin is associated with photoreceptor protection in retinal degeneration.

Retinal degeneration (RD) is a group of retinopathies characterized by progressive photoreceptor death and chronic neuroinflammation. Quercetin (QUE) is a natural flavonol with potent anti-inflammatory and free-radical scavenging properties. However, its protective effects against RD remain poorly characterized. This study aims to investigate the therapeutic potential of QUE on RD.In vitro and in vivo models of sodium iodate (NaIO3)-induced oxidative damage were used to evaluate the effects of QUE in RD. NaIO3 was used to induce oxidative damage in 661W cells. QUE was added to the cell cultures, and cell viability and oxidative markers were assessed. In vivo, QUE was delivered into the vitreous cavity of NaIO3-induced RD mice, followed by morphological analysis, visual function evaluation, behavioral testing, and Western blot detection.QUE protected 661W cells from NaIO3-induced oxidative damage by reducing intracellular reactive oxygen species, restoring mitochondrial membrane potential, and alleviating mitochondrial membrane pore disruption. In vivo, intravitreal QUE injection preserved retinal structure, reduced lesion area, elevated electroretinogram P-wave amplitude, and improved behavioral performance. QUE administration was accompanied by alleviated oxidative stress, inhibited glial activation, reduced pro-inflammatory cytokines, and elevated p-PI3K and p-AKT expression in RD. Neuroinflammation and oxidative stress are involved in RD pathology. These findings provide preliminary evidence that QUE exerts protective effects on photoreceptors in NaIO₃-induced RD. No causal relationship between PI3K/AKT activation and the retinal protection of QUE was established in this study.

Epigallocatechin gallate protects ARPE-19 cells in vitro and the retina in vivo by suppressing NF-κB p65-mediated ferroptosis.

The accumulation of ferrous ions and resulting oxidative stress within the retinal pigment epithelium triggers ferroptosis, leading to photoreceptor degeneration in dry age-related macular degeneration (dAMD), which is a disease currently without effective therapy. As ferroptosis has been identified as a molecular target of epigallocatechin-3-gallate (EGCG) in other diseases, this study aimed to investigate the protective role of EGCG and its mechanism against ferroptosis in NaIO3-induced ARPE-19 cell and RPE injury. We observed that iron overload disrupts iron homeostasis in both cellular and animal models, leading to RPE damage via ferroptosis activation. In ARPE-19 cells, EGCG attenuated NaIO3-induced injury by reducing Fe2+, MDA, and LDH levels, increasing GSH content, and upregulating SLC7A11 and GPX4 expression, effects which were equivalent to those produced by Fer-1. Mechanistically, EGCG exerted its anti-ferroptotic effect by binding strongly to NF-κB p65 and inhibiting its activation, consistent with the effects of the NF-κB inhibitor QNZ and NF-κB p65 silencing. In a dAMD model, EGCG administration suppressed ferroptosis, downregulated NF-κB p65 expression, and ameliorated RPE damage. In conclusion, these findings suggest that EGCG alleviates RPE damage associated with NF-κB p65-mediated ferroptosis, providing new insights into AMD pathogenesis and a promising therapeutic strategy.

Eugenol regulates ferroptosis through Mfn2/SLC7A11/GPX4 pathway to alleviate glutamate excitotoxicity damage in glaucoma.

Ginkgolide B protects retinal pigment epithelial cells from H2O2-induced oxidative stress and apoptosis by activating the AMPK/Nrf2 pathway

Objective To investigate whether Ginkgolide B (GB) protects retinal pigment epithelial cells (RPEs) from hydrogen peroxide (H2O2)-induced oxidative stress and apoptosis, and to explore the potential involvement of the adenosine monophosphate-activated protein kinase α (AMPKα)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. Methods Human RPEs were divided into the following groups: control, model (200 μmol/L H₂O₂ for 24 h), GB + H₂O₂, GB + H₂O₂ + Compound C (an AMPK inhibitor), H₂O₂ + Compound C, and GB alone. Cell viability, apoptosis, antioxidant parameters, and AMPKα/Nrf2 expression were assessed using the Cell Counting Kit-8 (CCK-8) assay, flow cytometry, colorimetric biochemical assays, transmission electron microscopy (TEM), quantitative polymerase chain reaction (PCR), and Western blot. Results TEM showed that GB attenuated H₂O₂-induced mitochondrial swelling and cristae disruption, which were reversed by Compound C. Compared with the model group, the GB + H₂O₂ group exhibited increased cell viability, decreased apoptosis, elevated activities of catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD), as well as increased glutathione (GSH) content, and reduced malondialdehyde (MDA) (all p < 0.05), though protein carbonyl (PC) levels showed no significant amelioration. All protective effects were attenuated by Compound C. In the GB-alone group, the percentage of apoptotic cells, Nrf2 mRNA expression, and all other parameters did not differ significantly from those in the control group. Conclusion GB was associated with protection of RPEs against H₂O₂-induced oxidative stress and apoptosis. Because these protective effects were attenuated by pharmacological inhibition of AMPK, the findings suggest that AMPK/Nrf2 signaling may contribute to the cytoprotective actions of GB. However, additional mechanistic studies are required to confirm the involvement of this pathway.

circKIAA1462 impaires autophagy and promotes pyroptosis in retinal pigment epithelium via the miR-183-5p/HMGB1 axis in diabetic retinopathy.

The cKIAA1462/miR-183-5p/HMGB1 axis plays a critical role in diabetic RPE injury by dual regulation of autophagy and pyroptosis by targeting this pathway may offer a novel therapeutic strategy for early diabetic retinopathy.

CircMETTL3 Inhibits H2O2‐Induced Senescence, Oxidative Stress, and DNA Damage in ARPE‐19 Cells via miR‐100/BMPR2 Axis

Background Age‐related macular degeneration (AMD) is a common degenerative eye disease that eventually leads to irreversible vision loss. CircRNAs have received increasing attention for their regulatory role in AMD. In this study, whole transcriptome sequencing identified differentially expressed circRNA (circMETTL3) in AMD. Previous studies have unlocked the potential mechanism of circMETTL3 in cancer, but its role in AMD has not been studied. Methods ARPE‐19 cells treated with H2O2 were used as the AMD cell model. The senescence, oxidative stress, and DNA damage of ARPE‐19 cells were determined by SA‐β‐gal staining, DCFH‐DA staining, and IF assay. The levels of RPE‐specific markers or mRNA levels were assessed using western blot assay. The potential mechanism of circMETTL3 was investigated by luciferase reporting assay and RIP assay. Results CircMETTL3 was revealed to decrease in AMD cell models. The addition of circMETTL3 decreased SA‐β‐gal staining and ROS production and facilitated cell viability in H2O2‐treated ARPE‐19 cells. Moreover, γH2AX and KRT18 levels were suppressed, and TJP1, BEST1, and CTNNB1 protein levels were increased by circMETTL3 addition. In addition, circMETTL3 could bind to and negatively regulate miR‐100. Overexpression of miR‐100 exacerbated senescence, oxidative stress, and DNA damage in H2O2‐treated ARPE‐19 cells, which reversed the effects of circMETTL3. Furthermore, BMPR2 was targeted by miR‐100. Overexpression of BMPR2 inhibited H2O2‐induced cell damage in ARPE‐19 cells, which reversed the effects of miR‐100. Conclusions In sum, these findings demonstrated that the circMETTL3/miR‐100/BMPR2 axis plays a vital regulatory role in AMD development.