Oxidative stress plays a critical role in the pathogenesis of retinal degeneration. Gypenosides are the major functional components isolated from Gynostemma pentaphyllum. They have been shown to protect against oxidative stress and inflammation and have also demonstrated a protective effect on experimental optic neuritis. In order to determine the protective properties of gypenosides against oxidative stress in human retinal pigment epithelium (RPE) cells, ARPE-19 cells were treated with HO or HO plus gypenosides for 24 h. ARPE-19 cells co-treated with gypenosides had significantly increased cell viability and decreased cell death rate when compared to cells treated with HO alone. The level of GSH, the activities of SOD and catalase, and the expression of NRF2 and antioxidant genes were notably decreased, while there were marked increases in ROS, MDA and pro-inflammatory cytokines in ARPE-19 cells exposed to HO; co-treatment with gypenosides significantly counteract these changes. Our study suggests that gypenosides protect RPE cells from oxidative damage and offer therapeutic potential for the treatment of retinal degeneration.

Age-related macular degeneration (AMD), the most common visual disorder in elderly people, is characterized by the formation of deposits beneath the retinal pigment epithelium (RPE) and by dysfunction of RPE and photoreceptor cells. The biologically active form of vitamin D, 1,25-(OH)2D3 (VITD), is categorized as a multifunctional steroid hormone that modulates many transcriptional processes of different genes and is involved in a broad range of cellular functions. Epidemiological and genetic association studies demonstrate that VITD may have a protective role in AMD, while single nucleotide polymorphisms in the vitamin D metabolism gene (CYP24A1) increase the risk of AMD. However, the functional mechanisms of VITD in AMD are not fully understood. In the current study, we investigated the impact of VITD on H2O2-induced oxidative stress and inflammation in human RPE cells. We demonstrate that exposure to H2O2 caused significantly reduced cell viability, increased production of reactive oxygen species (ROS), lowered expression of antioxidant enzymes and enhanced inflammation. VITD exposure notably counteracted the above H2O2-induced effects. Our data suggest that VITD protects the RPE from oxidative damage and elucidate molecular mechanisms of VITD deficiency in the development of AMD.

Mutations in the RPGR-interacting protein 1 (RPGRIP1) gene cause recessive Leber congenital amaurosis (LCA), juvenile retinitis pigmentosa (RP) and cone-rod dystrophy. RPGRIP1 interacts with other retinal disease-causing proteins and has been proposed to have a role in ciliary protein transport; however, its function remains elusive. Here, we describe a new zebrafish model carrying a nonsense mutation in the rpgrip1 gene. Rpgrip1homozygous mutants do not form rod outer segments and display mislocalization of rhodopsin, suggesting a role for RPGRIP1 in rhodopsin-bearing vesicle trafficking. Furthermore, Rab8, the key regulator of rhodopsin ciliary trafficking, was mislocalized in photoreceptor cells of rpgrip1 mutants. The degeneration of rod cells is early onset, followed by the death of cone cells. These phenotypes are similar to that observed in LCA and juvenile RP patients. Our data indicate RPGRIP1 is necessary for rod outer segment development through regulating ciliary protein trafficking. The rpgrip1 mutant zebrafish may provide a platform for developing therapeutic treatments for RP patients.

Acrylamide is a substance that can be neurotoxic in humans and experimental animals. It is formed at different rates in starchy foods cooked at temperatures above 120 °C as a result of interaction between monosaccharides and the amino acid asparagine. Carnosic acid accounts for over 90% of the antioxidant properties of rosemary extract and is a powerful inhibitor of lipid peroxidation in microsomal and liposomal systems. Carnosic acid has been shown to protect against oxidative and inflammatory effects. In order to investigate the protective properties of carnosic acid against acrylamide-induced toxicity in human retinal pigment epithelium (RPE) cells, ARPE-19 cells were pre-treated with 10 μM carnosic acid for 24 h followed by treatment with acrylamide (0.7 or 1 mM) for 24 h. ARPE-19 cells pre-treated with 10 μM carnosic acid showed significantly increased cell viability and decreased cell death rate when compared to ARPE-19 cells treated with acrylamide alone. Activities of SOD and catalase and the level of GSH and expression of NRF2 and a number of anti-oxidant genes were significantly decreased in ARPE-19 cells, while there were significant increases in ROS and MDA; pre-treatment with carnosic acid significantly counteracted these changes. Our results suggest that carnosic acid protected RPE cells from acrylamide-induced toxicity.