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.
Cynarin protects against oxidative stress-induced retinal degeneration by suppressing MAPK and NF-κB inflammatory signaling, representing a promising therapeutic candidate for preventing or delaying NaIO3-induced dry AMD-like retinal injury.
Yue-Lin Fang, Y. Hsu, Chao-Hsien Sung et al.· Biomolecules· 0 citations
Age-related Macular Degeneration (AMD), the leading cause of blindness worldwide, is a multifactorial disease with mitochondrial dysfunction recognized as an early pathogenic event. In our preclinical studies, we demonstrated that a single Cerium-Oxide Nanoparticles (CeO2-NPs) intravitreal injection in a light-induced degeneration model, was able to counteract the retinal degeneration. Our aim was to investigate whether neuroprotection activity could be correlated with mitochondrial morpho-functional preservation. Bulk transcriptomic profiling of whole retinal tissue revealed that light-induced retinal injury was associated with suppression of mitochondrial-related gene networks, including components of the electron transport chain and regulators of mitochondrial dynamics, whereas CeO2-NPs treatment restored the expression of antioxidant and mitochondrial biogenesis-related genes. Ultrastructural analysis by electron microscopy showed preservation of Retinal Pigmented Epithelial mitochondria's morphology and by high-resolution crystallographic analysis confirmed the intracellular localization of CeO2-NPs in proximity to mitochondria. Furthermore, Western blot analysis demonstrated that CeO2-NPs maintained mitophagy markers at basal levels, preventing excessive activation of mitochondrial quality-control pathways. Together, these findings support mitochondrial preservation as a key mechanism underlying nanoceria-mediated retinal neuroprotection and highlight CeO2-NPs as promising candidates for maintaining retinal homeostasis in AMD.
D. Zerti, L. Donato, Ignacio Babiloni Chust et al.· Nanomedicine: Nanotechnology...· 0 citations
Background: Diabetic retinopathy (DR) is a leading cause of vision loss, with oxidative stress and inflammation serving as critical drivers of its onset and progression. Curcumin, a natural polyphenol, is known for its potent anti-inflammatory and antioxidant properties. Glial fibrillary acidic protein (GFAP) is commonly used as an indicator of retinal macroglial reactivity, whereas the NLRP3 inflammasome is an important mediator of inflammatory signaling in DR. We evaluated retinal vascular abnormalities and retinal GFAP immunoreactivity and examined whether these findings were accompanied by changes in retinal NLRP3 and IL-1β protein abundance and in the levels of cleaved caspase-1 and cleaved GSDMD. Methods: Diabetes was induced in 7-week-old rats via a single intraperitoneal injection of streptozotocin. Following the confirmation of hyperglycemia, curcumin was administered orally. To evaluate the effects, we performed trypsin digestion, haematoxylin and eosin (H&E) staining, fluorescein isothiocyanate (FITC)–dextran permeability assays, immunofluorescence staining, and Western blotting on the harvested retinas. Results: The DM group showed increased acellular capillary formation, vascular leakage, retinal GFAP immunoreactivity, NLRP3 and IL-1β protein abundance, and levels of cleaved caspase-1 and cleaved GSDMD. Compared with the untreated DM group, the DM + curcumin group showed lower values for all of these outcomes. Conclusions: In diabetic rats, oral administration of a curcumin-containing formulation was associated with fewer retinal vascular abnormalities and lower GFAP immunoreactivity, accompanied by parallel differences in inflammasome-related proteins. These findings support the potential of this formulation as an adjunctive therapeutic approach for early diabetic retinopathy.
Hyoseon Yu, J. Kang, Seo Hyun Kim et al.· Life· 0 citations
EGb 761 exerts a protective effect on photoreceptor cell damage in retinal degeneration and is associated with a modification of the AMPK/ERK signaling pathway that regulates oxidative stress and autophagy.
Qiu-ye Teng, M. Chudhary, Wenkang Dong et al.· Current Eye Research· 0 citations
Introduction: Diabetic retinopathy (DR) is characterized by early retinal neurodegeneration accompanied by progressive alterations of the retinal microvasculature, both exacerbated by hyperglycemia-induced oxidative stress and inflammation. Mitochondrial dysfunction critically contributes to neuronal loss and vascular impairment. The 18 kDa Translocator Protein (TSPO) is a mitochondrial outer membrane protein whose expression is increased in activated retinal glial cells and represents a promising target to modulate neuroinflammation and oxidative stress. This study evaluates the therapeutic potential of the TSPO ligand PIGA-1138 in experimental models of DR. Methods: PIGA-1138 (3 µM in vitro; 10 mg/kg/day, i.p., in vivo) was evaluated in high glucose (HG)-exposed 661W retinal cells and in streptozotocin (STZ, 150 mg/kg)-induced diabetic C57BL/6J mice. Cell viability, mitochondrial function, oxidative stress, and Nrf2, HO-1, and SOD1 expression were assessed in vitro. Retinal function and morphology were evaluated in vivo by electroretinography (ERG), visual acuity testing, and optical coherence tomography (OCT) at 30 and 60 days after diabetes induction. Results: PIGA-1138 significantly improved cell viability, reducing apoptosis (TUNEL p ≤ 0.01), preserving mitochondrial membrane potential (MitoRed p ≤ 0.01), reducing oxidative damage, and enhancing Nrf2 nuclear translocation together with HO-1 (p ≤ 0.05) and SOD1 (p ≤ 0.01) expression in HG-treated retinal cells. In diabetic mice, treatment preserved ERG responses and limited retinal thinning at 60 days (p ≤ 0.01), while showing a trend toward preserving visual acuity. Conclusions: Targeting mitochondrial TSPO with PIGA-1138 attenuates key hallmarks of DR by mitigating oxidative stress, suppressing neuroinflammation, and preserving retinal structure and function. These findings support TSPO as a potential disease-modifying target for DR.
Ocular diseases are a significant public health problem worldwide and represent one of the leading causes of disability. The prevalence of visual impairment is steadily increasing, largely driven by the ageing population. Oxidative stress, chronic inflammation and neurodegenerative processes underlie the pathogenesis of many eye diseases, including age-related macular degeneration (AMD), diabetic retinopathy, glaucoma, and cataracts, contributing to progressive vision loss and functional impairment. Carotenoids such as lutein, zeaxanthin, meso-zeaxanthin, β-carotene, lycopene, and astaxanthin exhibit multidirectional biological effects, including antioxidant, anti-inflammatory, and neuroprotective properties. These compounds are selectively accumulated in the tissues of the eye, especially in the retina and macula, where they neutralise reactive oxygen species, modulate inflammatory pathways, stabilise mitochondrial function and support the survival and function of retinal ganglion cells and photoreceptors. The aim of our review was to provide a comprehensive review of current data regarding the mechanisms of action of carotenoids and their potential clinical significance in the prevention and treatment of retinal, optic nerve, lens, and eye surface diseases, including dry eye syndrome and Meibomian gland dysfunction. We identified results of available experimental and clinical research and outlined that an adequate supply of carotenoids in the diet or in the form of supplementation may support the protection of eye structures against oxidative and inflammatory damage, improve visual performance and potentially slow disease progression. However, high-quality prospective clinical trials are necessary to conclusively assess their therapeutic efficacy and establish evidence-based recommendations for clinical practice.