Glycitin Primes Retinal Pigment Epithelium Resilience to High-Glucose Injury via the PI3K/AKT Pathway

Diabetic retinopathy (DR) is a leading cause of vision loss, which is driven in part by oxidative stress-induced dysfunction of ocular tissues. We previously showed that high glucose conditions trigger senescence pathways and damage the retinal pigment epithelium (RPE). Here, we identify glycitin, a natural isoflavone, as a candidate cytoprotectant and define its mechanism of action in high glucose-exposed ARPE-19 cells. Using RNA-seq followed by Ingenuity Pathway Analysis, we mapped glycitin-responsive programs and validated key nodes experimentally. Glycitin partially restored cell proliferation, suppressed oxidative stress, and reversed high glucose-induced premature senescence, primarily through modulation of the PI3K/AKT pathway. These findings suggest that glycitin could be a promising modulator of RPE resilience and support its further development for preventing or treating DR and other types of retinal degeneration.