Roles of CCN5 in Retinal Pigment Epithelium

Abstract

Age-related macular degeneration (AMD) is a retinal degenerative disease that leads to irreversible vision loss in people older than 50 years of age. AMD is divided into two types; dry type AMD (atrophic or non-neovascular AMD) and wet type AMD (neovascular AMD; nAMD). nAMD is characterized by choroidal neovascularization (CNV), the growth of abnormal blood vessels into macular. Therefore, anti-vascular endothelial growth factor (VEGF) therapy is used as a golden standard for nAMD treatment. However, a significant portion of nAMD patients already have subretinal fibrosis and they couldn’t get improved visual acuity after anti-VEGF therapy. Even, subretinal fibrosis develops in over 40% of nAMD patients who received anti-VEGF therapy. Subretinal fibrosis is tightly associated with epithelial-mesenchymal transition (EMT) of retinal pigment epithelium (RPE). RPE is a monolayer of cuboidal cells located between photoreceptors and choroid. RPE have highly polarized morphology including apical microvilli and integrated tight junctions. RPE performs various functions related to visual function including the formation of a blood-retinal barrier that regulates epithelial transport and inhibits the infiltration of new blood vessels into the retina, support of photoreceptor function, control of the visual cycle, and phagocytosis. Dysfunction of RPE causes severe vision loss. EMT of RPE occurs RPE dysfunction and it leads to severe vision loss. In this study, I tested whether co-treatment of CCN5 which is an anti-fibrotic protein, and anti-VEGF drugs can be a safer therapeutic modality for nAMD via inhibition of fibrosis induced by anti-VEGF drugs and CCN5 that also have anti-angiogenic effects can be an effective and safe therapeutic modality for nAMD via inhibition of CNV and fibrosis simultaneously.