PDZK1 Protects Against RPE Senescence by Targeting the 14-3-3ε-mTOR Axis to Attenuate Early Diabetic Retinopathy.

ABSTRACT: Diabetic retinopathy (DR) is the leading cause of blindness among working-age adults, yet its pathogenesis remains incompletely understood. The retinal pigment epithelium (RPE) plays a vital role in maintaining retinal homeostasis. In this study, the expression of senescence marker protein p16 is observed to be upregulated in the RPE of early DR mouse models. Transcriptomic profiling reveals that PDZ domain protein 1 (PDZK1) expression is downregulated in RPE cells after 48 hours of high-glucose stimulation. Overexpression of PDZK1 reduces senescence markers in RPE cells, promoting cell proliferation and transport functions. Mechanistically, PDZK1 alleviates RPE cell senescence by interacting with 14-3-3ε to regulate the mTOR pathway, which is closely related to reducing oxidative stress a

SUBMITTER: Zhao J 

PROVIDER: S-EPMC12631858 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature