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

In diabetic retinopathy (DR), hyperglycemia induces retinal pigment epithelium (RPE) cell senescence via downregulation of PDZK1. PDZK1 overexpression counteracts senescence by binding 14-3-3ε to modulate mTOR signaling, reducing oxidative stress and enhancing autophagy. Both genetic PDZK1 restoration and pharmacologic senolysis (Nutlin-3a) attenuate retinal senescence and ameliorate early DR pathology, establishing the PDZK1-14-3-3ε-mTOR axis as a therapeutic target Cells were cultured for 48 hours in either control medium containing 5.5 mM D-glucose and 32 mM mannitol, or in high-glucose (HG) medium containing 37.5 mM D-glucose, followed by RNA extraction for sequencing.