Background: Age-related macular degeneration (AMD) is the leading cause of blindness, and is associated with oxidative stress and the development of new blood vessels. At present, the main clinical treatment for AMD includes intraocular injection of vascular endothelial growth factor (VEGF). However, treatment includes repeated injections with significant side-effects. Therefore, new treatment options are required. The aim of the present study was to discover the new treatment target of AMD from the gene level. Methods: The Gene Expression Omnibus (GEO) database was used to analyze the differential gene expression in AMD, and the regulator of G-protein signaling 1 (RGS1) was obtained by bioassay. Western blotting and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were used to detect the expression levels of RGS1, VEGF, and other related molecules in human microvascular endothelial cells (HMECs) under different conditions. Cell viability, apoptosis, and proliferation of HMECs were measured by Cell Counting Kit-8 proliferation assay. Immunofluorescence and immunohistochemistry detected the interaction between RGS1, platelet endothelial cell adhesion molecule-1, and VEGF. Results: RGS1 was found to closely associated with the proliferation of vascular endothelial cells, and therefore, with angiogenesis. The expression of RGS1, VEGF, and platelet endothelial cell adhesion molecule-1 was upregulated in laser model mice and hypoxia model HMECs. Knockout of RGS1 inhibits the expression of VEGF and HMEC proliferation, thereby inhibiting AMD angiogenesis. Conclusions: Our results support the use of RGS1 as a new potential target for the future treatment of AMD.

Purpose Proliferative vitreoretinopathy (PVR) is a disease process resulting from proliferation of retinal pigment epithelial (RPE) cells in the vitreous and periretinal area, leading to periretinal membrane formation and traction and eventually to postoperative failure after vitreo-retinal surgery for primary rhegmatogenous retinal detachment (RRD). The present study was designed to test the therapeutic potential of a p21CIP/WAF1 (p21) inducing saRNA for PVR. Methods A chemically modified p21 saRNA (RAG1-40-53) was tested in cultured human RPE cells for p21 induction and for the inhibition of cell proliferation, migration and cell cycle progression. RAG1-40-53 was further conjugated to a cholesterol moiety and tested for pharmacokinetics and pharmacodynamics in rabbit eyes and for therapeutic effects after intravitreal administration in a rabbit PVR model established by injecting human RPE cells. Results RAG1-40-53 (0.3 mg, 1 mg) significantly induced p21 expression in RPE cells and inhibited cell proliferation, the progression of cell cycle at the G0/G1 phase and TGF-β1 induced migration. After a single intravitreal injection into rabbit eyes, cholesterol-conjugated RAG1-40-53 exhibited sustained concentration in the vitreal humor beyond at least 8 days and prevented the progression of established PVR. Conclusion p21 saRNA could represent a novel therapeutics for PVR by exerting a antiproliferation and antimigration effect on RPE cells.