Search Results (98)

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

The Mediterranean diet, rich in plant-based foods, healthy fats, and herbs, has long been associated with a range of health benefits, including cardiovascular, neuroprotective, and anti-inflammatory effects. Recent studies suggest that certain components of this diet, particularly spices such as bay laurel, thyme, oregano, sage, and rosemary, may play a critical role in protecting the retina from oxidative damage, a key factor in blue-light-induced retinal degeneration. Blue light, emitted by digital screens and artificial lighting, has been implicated in the development of retinal conditions like age-related macular degeneration by inducing oxidative stress and inflammation. This review explores the potential of the herbs and spices commonly present in the Mediterranean diet to mitigate blue-light-induced retinal damage. These herbs are rich in polyphenols, flavonoids, essential oils, and terpenes, which offer antioxidant, anti-inflammatory, and antimicrobial properties, contributing to retinal health and reducing oxidative damage. By focusing on bioactive compounds such as eucalyptol (1,8-cineole), rosmarinic acid, carnosic acid, eugenol, and thymol, this article investigates how these herbs and spices might act as natural protectants against blue-light-induced stress and retinal degeneration. The findings highlight the promising role of these culinary staples in preventing retinal damage and offer insights into future dietary recommendations for eye health in an increasingly digital world. Full article

Background: The retina plays a vital role in vision, and its impairment can cause significant visual deficits. Current retinal disease treatments range from conventional anti-inflammatory drugs to advanced anti-VEGF therapies and monoclonal antibodies. TnP, a novel synthetic peptide in preclinical development, has demonstrated therapeutic potential in chronic inflammatory conditions such as multiple sclerosis and asthma due to its immunomodulatory properties. Using zebrafish—which share significant genetic homology with humans—we investigated TnP’s effects on retinopathy models mimicking diabetic retinopathy (DR) through either cobalt chloride (CoCl₂)-induced hypoxia or light-induced retinal damage (LIRD). Methods: We employed two retinal injury models (CoCl₂-induced hypoxia and LIRD) and subjected them to TnP treatment, assessing the outcomes through visual–motor response testing and histological examination. Results: CoCl₂ exposure impaired swimming activity, while light damage reduced the movement distance. Both models induced distinct retinal morphological changes. Although TnP failed to reverse most injury effects, it specifically restored the inner plexiform layer (IPL)’s thickness. Conclusions: Our findings suggest that TnP may enhance neuronal plasticity by promoting cell proliferation and synaptic connectivity. While showing promise as a therapeutic candidate for retinal and neurodegenerative disorders, TnP might achieve optimal efficacy when combined with complementary treatments. Full article

Myo/Nog cells play a pivotal role in ocular development and demonstrate a rapid response to stress and injury. This study investigates their behavior and distribution in a murine model of retinitis pigmentosa, specifically in C3H/HeJ mice, which exhibit photoreceptor degeneration due to a homozygous mutation in the Pde6brd1 gene. Retinal samples from C3H/HeJ and C57BL/6J mice were analyzed at postnatal weeks 2.5 to 6 using hematoxylin and eosin staining, immunofluorescence for brain-specific angiogenesis inhibitor 1 (BAI1) expressed in Myo/Nog cells, and TUNEL labeling for apoptotic cell detection. The results demonstrated a progressive thinning of the outer nuclear layer (ONL) in C3H mice, accompanied by a significant increase in Myo/Nog cell numbers. In normal retinas, Myo/Nog cells were primarily located in the inner nuclear and outer plexiform layers. However, in C3H/HeJ mice, they accumulated in the ONL near apoptotic photoreceptors and within the choroid. Notably, in these degenerative regions, Myo/Nog cells exhibited features of phagocytosis, suggesting a role in apoptotic cell clearance. Additionally, parallels between Myo/Nog cell responses in retinitis pigmentosa and models of oxygen-induced retinopathy, ocular hypertension, and light damage suggest that these cells may be leveraged for therapeutic purposes. Full article

Although melanin is viewed as a natural sunscreen that protects pigmented cells against the adverse effects of solar radiation, recent studies have demonstrated that, under certain conditions, the pigment can actually contribute to light-induced oxidative damage of the cells. However, the main issue with such studies is finding natural pigments without photooxidative modifications. Recently, melanin obtained from melanocytes, generated from human induced pluripotent stem cells (hiPSC-Mel), was suggested as a promising source of the pigment without significant photooxidation. Although different studies have demonstrated the feasibility of the above-mentioned technique to obtain melanin-producing cells, no thorough analysis of the physicochemical properties of the pigment has been performed. To address this issue, we examined the key physicochemical parameters, including the aerobic photoreactivity of melanin isolated from hiPSC-Mel and compared them with those of melanin from other known sources of the pigment, such as bovine retinal pigment epithelium (bRPE) and phototype V (PT-V) hair. Electron paramagnetic resonance (EPR) spectroscopy, dynamic light scattering, UV–Vis absorption and HPLC analysis of melanin degradation products were used. The ability of the examined melanins to photogenerate reactive oxygen species was determined by employing EPR oximetry, EPR spin-trapping and time-resolved singlet oxygen phosphorescence. Although the results of such measurements demonstrated that melanin obtained from hiPSC-Mel exhibited the physicochemical properties typical for eumelanin, a contribution from pheomelanin with a substantial presence of benzothiazine subunits, was also evident. Importantly, the hiPSC-Mel pigment had significantly lower photoreactivity compared to bRPE melanin and PT-V hair melanin. Our findings indicate that hiPSC-Mel could be an excellent source of high-quality pigment for photoprotection studies. Full article

Shinorine is a mycosporine-like amino acid isolated from laver (Porphyra dentata), and interest in its functionality has increased recently due to increased production using yeast. There have been few reports on the pharmacological activity of shinorine, and we sought to find the pharmacological significance of shinorine. In the present study, we investigated the pharmacological effects of shinorine purified from Porphyra dentata on ARPE-19 cells. First, when ARPE-19 cells were treated with bis-retinoid N-retinyl-N-retinylidene ethanolamine (A2E) and blue light (BL), cytotoxicity increased, and apoptosis was observed. We investigated the effects of shinorine on A2E- and BL-induced cytotoxicity and changes in apoptotic factors, inflammation, and carbonyl stress. A2E and BL exposure increased ARPE-19 cell apoptosis, but this increase was attenuated by shinorine in a concentration-dependent manner. Treatment with A2E and BL induced ARPE-19 cell apoptosis, but treatment with shinorine decreased the apoptotic factors, such as MAPKs. Shinorine reduced p-JNK and p-P38, which were increased by A2E and BL. In addition, shinorine was found to regulate inflammatory proteins and proteins associated with carbonyl stress. In conclusion, shinorine may suppress cell damage caused by A2E treatment and BL exposure at the cellular level by regulating various cell death and inflammatory response pathways. Full article

The widespread use of light-emitting diodes (LEDs) has increased blue light (BL) exposure, raising concerns about its potential adverse effects on ocular health. Prolonged exposure to BL has been implicated in the pathogenesis of various retinal disorders, including age-related macular degeneration (AMD), primarily through mechanisms involving oxidative stress and inflammation mediated by the overproduction of reactive oxygen species (ROS). This review synthesizes current evidence on the photoprotective properties of dietary bioactive compounds, (e.g., anthocyanins, curcumin, quercetin, myricetin, and resveratrol), with a focus on their potential to mitigate BL-induced retinal damage. Accumulating research suggests that dietary antioxidants, particularly polyphenols, may offer photoprotective benefits. These phytochemicals act by neutralizing ROS and enhancing the retina’s endogenous antioxidant capacity. Based on these findings, this review advocates for a food-first approach in future investigations, emphasizing the development of evidence-based dietary recommendations to bolster retinal health and mitigate the risk of BL-related ocular diseases. Considering the current lack of empirical clinical studies examining the impact of BL on human ocular health, future research in the field of BL hazard should prioritize two key approaches: conducting large-scale epidemiological dietary surveys and implementing clinical trials on functional ingredients that have demonstrated beneficial effects against photodamage in preclinical animal studies. Full article

Background/Objectives: Neurodegenerative ocular diseases, such as age-related macular degeneration (AMD) and glaucoma, represent growing public health concerns. Oxidative stress plays a key role in their development, damaging retinal cells and accelerating disease progression. Melatonin (Mel) is a potent antioxidant with neuroprotective properties; however, it faces limitations such as low solubility. This study proposes the use of human serum albumin nanoparticles (Np-HSA) to enhance the delivery of Mel to the posterior segment of the eye and evaluates its neuroprotective and anti-apoptotic effects on the retina. Methods: A model of retinal degeneration was induced in New Zealand albino rabbits using cytotoxic and oxidative agents. Np-HSA-Mel nanoparticles were administered subconjunctivally, and cellular viability and retinal functionality were assessed using flow cytometry and pupillary light reflex (PLR). Histological and immunohistochemical studies, including the TUNEL assay, were performed to analyse cell survival and apoptotic index. Results: Np-HSA-Mel significantly preserved pupillary function and cell viability, demonstrating lower apoptosis compared to Mel solution and Np-HSA alone. Histologically, eyes treated with Np-HSA-Mel exhibited fewer structural alterations and greater cellular organisation. The TUNEL assay confirmed a significant reduction in the apoptotic index of retinal ganglion cells (RGCs) treated with Np-HSA-Mel. Conclusions: Np-HSA-Mel effectively overcame ocular barriers, achieving greater neuroprotective efficacy at the retinal level. These findings highlight the synergistic potential of albumin and Mel in treating neurodegenerative ocular diseases, opening new perspectives for future therapies. Full article

Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal diseases characterized by the progressive loss of photoreceptor function, visual impairment, and, ultimately, blindness. While gene therapy has emerged as a promising therapy, it is currently available only for the RPE65 gene mutation, leaving many patients without targeted genetic treatments. Non-surgical interventions may help in managing the progression of RP and improving patients’ quality of life. Visual training and rehabilitation, maximizing residual vision, have shown potential in improving mobility and patients’ ability to perform daily activities. Visual aids enhance visual function. Moreover, photo-protection demonstrated effectiveness in mitigating light-induced damage and improving visual comfort. Alternative therapies (i.e., electrostimulation, acupuncture, and ozone therapy) are being explored to preserve retinal function and reduce disease progression. Pharmacological interventions supported by nutritional and psychological counseling play a role in slowing retinal degeneration while managing the emotional burden of progressive vision loss. Although for these interventions, further validation is required, their potential benefits make them valuable additions to care for RP patients. The integration of these interventions into a multidisciplinary care approach—including ophthalmologists, orthoptist, dietitians, and psychologists—is essential for providing comprehensive, personalized care to RP patients while awaiting more widespread gene therapy solutions. Full article

All-trans-retinal (atRAL)-induced photoreceptor atrophy and retinal degeneration are hallmark features of dry age-related macular degeneration (AMD) and Stargardt disease type 1 (STGD1). The toxicity of atRAL is closely related to the generation of reactive oxygen species (ROS). Quercetin, a natural product, is known for its potent antioxidant properties; however, its effects in mitigating atRAL-mediated retinal damage remains unclear. This study investigated the protective effects of quercetin against atRAL-induced photoreceptor damage. Using atRAL-loaded 661W photoreceptor cells, we evaluated cell viability, ROS generation, and endoplasmic reticulum (ER) stress under quercetin treatment. Quercetin significantly restored the cell viability (to 70%) and reduced ROS generation in atRAL-treated 661W cells. Additionally, Western blot analysis demonstrated that quercetin mitigated protein kinase RNA-like ER kinase (PERK) signaling, preventing ER stress-induced apoptosis. Importantly, in Abca4^−/−Rdh8^−/− mice, an animal model of light-induced atRAL accumulation in the retina, quercetin treatment effectively alleviated light-exposed photoreceptor atrophy and retinal degeneration by attenuating PERK signaling. Thus, quercetin protected photoreceptor cells from atRAL-induced damage by inhibiting ROS generation and PERK signaling, which suggests its potential as a therapeutic agent for atRAL-related retinal degeneration. Full article

Reactive oxygen species (ROS) play a pivotal role in apoptosis. We reported that Blue Light (BL) induced oxidative stress in human retinal pigment epithelial (RPE) cells in vitro and increased drusen deposition and RPE cell apoptosis in human eyes. Here, we investigated the mechanisms underlying BL-induced damage to RPE cells. Cells were exposed to BL with or without the antioxidant N-acetylcysteine. Cells were analyzed for levels of ROS, proliferation, viability, and mitochondria membrane potential (ΔΨ_M) fluctuation. We performed proteomic analyses to search for differentially expressed proteins. ROS levels increased following RPE cell exposure to BL. While ROS production did not affect RPE cell proliferation, it was accompanied by decreased ΔΨ_M and increased cell apoptosis due to the caspase cascade activation in a ROS-dependent manner. Proteomic analyses revealed that BL decreased the levels of ROS detoxifying enzymes in exposed cells. We conclude that BL-induced oxidative stress is cytotoxic to RPE cells. These findings bring new insights into the involvement of BL on RPE cell damage and its role in the progression of age-related macular degeneration. The use of antioxidants is an avenue to block or delay BL-mediated RPE cell apoptosis to counteract the disease progression. Full article

Blue light accelerates retinal aging. Previous studies have indicated that wavelengths between 400 and 455 nm are most harmful to aging retinal pigment epithelia (RPE). This study explored whether filtering these wavelengths can protect cells exposed to broad sunlight. Primary porcine RPE cells loaded with 20 µM A2E were exposed to emulated sunlight filtered through eye media at 1.8 mW/cm² for 18 h. Filters selectively filtering out light over 400–455 nm and a dark-yellow filter were interposed. Cell damage was measured by apoptosis, hydrogen peroxide (H₂O₂) production, and mitochondrial membrane potential (MMP). Sunlight exposure increased apoptosis by 2.7-fold and H₂O₂ by 4.8-fold, and halved MMP compared to darkness. Eye Protect System^TM (EPS) technology, filtering out 25% of wavelengths over 400–455 nm, reduced apoptosis by 44% and H₂O₂ by 29%. The Multilayer Optical Film (MOF), at 80% of light filtered, reduced apoptosis by 91% and H₂O₂ by 69%, and increased MMP by 73%, overpassing the dark-yellow filter. Photoprotection increased almost linearly with blue-violet light filtering (400–455 nm) but not with total blue filtering (400–500 nm). Selective filters filtering out 25% (EPS) to 80% (MOF) of blue-violet light offer substantial protection without affecting perception or non-visual functions, making them promising for preventing light-induced retinal damage with aesthetic acceptance for permanent wear. Full article

The purpose of this study was to investigate the protective effects of 7S,15R-dihydroxy-16S,17S-epoxy-docosapentaenoic acid (diHEP-DPA) in retinal pigment epithelial (RPE) cell damage. ARPE-19 cells, a human RPE cell line, were cultured with diHEP-DPA and Bis-retinoid N-retinyl-N-retinylidene ethanolamine (A2E), followed by exposure to BL. Cell viability and cell death rates were determined. Western blotting was performed to determine changes in apoptotic factors, mitogen-activated protein kinase (MAPK) family proteins, inflammatory proteins, and oxidative and carbonyl stresses. The levels of pro-inflammatory cytokines in the culture medium supernatants were also measured. Exposure to A2E and BL increased the ARPE-19 cell death rate, which was alleviated by diHEP-DPA in a concentration-dependent manner. A2E and BL treatments induced apoptosis in ARPE-19 cells, which was also alleviated by diHEP-DPA. Analysis of the relationship with MAPK proteins revealed that the expression of p-JNK and p-P38 increased after A2E and BL treatments and decreased with exposure to diHEP-DPA in a concentration-dependent manner. DiHEP-DPA also affected the inflammatory response by suppressing the expression of inflammatory proteins and the production of pro-inflammatory cytokines. Furthermore, it was shown that diHEP-DPA regulated the proteins related to oxidative and carbonyl stresses. Taken together, our results provide evidence that diHEP-DPA can inhibit cell damage caused by A2E and BL exposure at the cellular level by controlling various pathways involved in apoptosis and inflammatory responses. Full article

Blue light is the higher-energy region of the visible spectrum. Excessive exposure to blue light is known to induce oxidative stress and is harmful to the eyes. The stems of Dendrobium nobile Lindl. (Orchidaceae), named Jinchaishihu, have long been used in traditional Chinese medicine (TCM) for nourishing yin, clearing heat, and brightening the eyes. The polysaccharide is one of the major components in D. nobile. However, the effect on ocular cells remains unclear. This study aimed to investigate whether the polysaccharide from D. nobile can protect the eyes from blue light-induced injury. A crude (DN-P) and a partially purified polysaccharide (DN-PP) from D. nobile were evaluated for their protective effects on blue light-induced damage in ARPE-19 and 661W cells. The in vivo study investigated the electroretinographic response and the expression of phototransduction-related genes in the retinas of a Drosophila model. The results showed that DN-P and DN-PP could improve blue light-induced damage in ARPE-19 and 661W cells, including cell viability, antioxidant activity, reactive oxygen species (ROS)/superoxide production, and reverse opsin 3 protein expression in a concentration-dependent manner. The in vivo study indicated that DN-P could alleviate eye damage and reverse the expression of phototransduction-related genes, including ninaE, norpA, Gαq, Gβ76C, Gγ30A, TRP, and TRPL, in a dose-dependent manner in blue light-exposed Drosophila. In conclusion, this is the first report demonstrating that D. nobile polysaccharide pretreatment can protect retinal cells and retinal photoreceptors from blue light-induced damage. These results provide supporting evidence for the beneficial potential of D. nobile in preventing blue light-induced eye damage and improving eyesight. Full article

Retinitis pigmentosa is a common cause of inherited blindness in adults, which in many cases is associated with an increase in the formation of reactive oxygen species (ROS) that induces DNA damage, triggering Poly-ADP-Ribose Polymerase 1 (PARP1) activation and leading to parthanatos-mediated cell death. Previous studies have shown that resveratrol (RSV) is a promising molecule that can mitigate PARP1 overactivity, but its low bioavailability is a limitation for medical use. This study examined the impact of a synthesized new acylated RSV prodrug, piceid octanoate (PIC-OCT), in the 661W cell line against H₂O₂ oxidative stress and in rd10 mice. PIC-OCT possesses a better ADME profile than RSV. In response to H₂O₂, 661W cells pretreated with PIC-OCT preserved cell viability in more than 38% of cells by significantly promoting SIRT1 nuclear translocation, preserving NAD⁺/NADH ratio, and suppressing intracellular ROS formation. These effects result from expressing antioxidant genes, maintaining mitochondrial function, reducing PARP1 nuclear expression, and preventing AIF nuclear translocation. In rd10 mice, PIC-OCT inhibited PAR-polymer formation, increased SIRT1 expression, significantly reduced TUNEL-positive cells in the retinal outer nuclear layer, preserved ERGs, and enhanced light chamber activity (all p values < 0.05). Our findings corroborate that PIC-OCT protects photoreceptors by modulating the SIRT1/PARP1 axis in models of retinal degeneration. Full article