Oxidative stress is a major contributor to retinal degenerative diseases such as age-related macular degeneration (AMD). Methionine sulfoxide reductase A (MsrA) is an antioxidant enzyme that is naturally expressed in the retinal pigment epithelium (RPE), where it supports retinal tissue repair. Its loss can impair visual function and contribute to photoreceptor degeneration.
Our researchers developed a novel gene therapy approach for retinal degeneration using both Adeno-Associated Virus (AAV) and Lentiviral (Lenti) vectors to deliver and express MsrA in retinal cells.. The AAV-MsrA vector is ideal for transient, high-efficiency expression in preclinical and clinical models. The Lenti-MsrA vector enables stable, long-term expression in RPE cells, suitable for chronic conditions. Treatment of human RPE cells, ARPE-19 cells, expressing MsrA with oxidative stress inducers—Paraquat and Ferric Ammonium Citrate (FAC)- showed an increase in cell viability demonstrating enhanced survival under oxidative stress.
WST-1 assay showing increase in cell viability upon lenti-MsrA expression as compared to control cells against Paraquat induced oxidative stress. Significant protection of ARPE cells was observed when stable cells were incubated with 250 and 500 μM of Paraquat. Values are reported as average ± SD. (***P<0.005 and **P<0.05, N=5)