The Protection and Possible Innate Pathways of Autophagy Inducers on High-Glucose Stressed Retinal Pigment Epithelium and Rat Model
Description: Like Age-related macular degeneration (AMD), diabetic retinopathy is one of the major causes of adult visual loss in developed countries. Although the exact pathogenesis is uncertain, RPE has been implicated in the early pathogenesis of both. In patients with long term diabetic retinopathy, retinal pigment epithelium degeneration progressed even if the other conditions were well controlled and the retinopathy stable. It is speculated to be the results of RPE apoptosis caused by oxidative damage, such as the condition of dry-type AMD. Retinal pigment epithelium (RPE) is a single layer of epithelial cells lining the posterior segment of the eye. It is located between the light-sensing photoreceptors and the choriocapillaris. RPE cells serve a variety of important functions protecting and maintaining the function of the visual function. A failure of any one of these functions can lead to degeneration of the retina, loss of visual function, and blindness. Recent studies underline the involvement of inflammation, oxidative stress, and autophagy in the pathogenesis of diabetic retinopathy. Autophagy has been shown to involve in both exacerbation and alleviation of DR. Our previous study results suggest that erb-b2 receptor tyrosine-protein kinase 2 (ERBB2) may play an important role in modulating autophagic RPE cell death during oxidative stress. Recent study also showed that autophagy inducers rapamycin and metformin diminish vital dye-induced retinal damage in vivo through activation of autophagy. The purpose of this study is to further investigate the possible protective effect of these autophagy inducers against oxidative damage by hydrogen peroxide (H2O2) in retinal pigment epithelium stressed by hyperglycemia. Based on the results from the first year, we will have further study in the high glucose animal model at the second year. In vitro studies will be repeated by using primary RPE cell culture from a high glucose animal model. The protective effects will be then tested in vivo by using the implantation of osmotic minipump containing experimental agents or placebo. The project will clarify the mechanism that autophagy inducer-mediated protective effects to high-glucose induced damage of RPE, which will benefit the prevention and the treatment of diabetic retinopathy in the future.
Amount: TWD 970,000
Funding type: research
Funder scheme: 學術補助
Investigators: 許淑娟, 邱建智
Institution: 高雄醫學大學醫學系眼科
Funded outputs count: 2
Funder award ID: MOST109-2314-B037-024
OpenAlex ID: G900561083