ASNS Regulates H2O2-Induced Senescence, Oxidative Stress, and Glucose Metabolism in ARPE-19 Cells by Modulating USP13 Expression.

Age-related macular degeneration (AMD) is a common degenerative disease of the eye that ultimately leads to irreversible vision loss. Asparagine synthase (ASNS) is an aminotransferase, and its low expression is associated with retinal damage. The present study centered on the protective effect of ASNS on retinal epithelial cells. We found that in the AMD cell model, overexpression of ASNS reduced SA-β-gal staining and ROS production, and increased cell viability in H2O2-treated ARPE-19 cells. In addition, overexpression of ASNS increased glucose consumption, lactate production, extracellular acidification rate (ECAR), and oxygen consumption rate (OCR) and enhanced the expression of glycolytic markers. Molecular mechanistic studies revealed that ASNS was highly bound to USP13 protein and increased USP13 expression. Furthermore, ASNS protected the retinal epithelium from oxidative stress damage in an animal model of AMD. Taken together, these findings suggest that the ASNS/USP13 axis plays an important regulatory role in AMD development. Our findings not only emphasized the understanding of the role of glucose metabolism in AMD, but also identified a promising target for future AMD therapy.