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

Area of Science:

• Ophthalmology
• Cell Biology
• Molecular Medicine

Background:

• Diabetic retinopathy (DR) is a leading cause of blindness.
• The pathogenesis of DR, particularly the role of retinal pigment epithelium (RPE) cell senescence, is not fully understood.

Purpose of the Study:

• Investigate the role of RPE cell senescence in DR.
• Identify molecular mechanisms regulating RPE cell senescence in DR.
• Explore therapeutic strategies targeting RPE senescence for DR.

Main Methods:

• Utilized early-stage DR mouse models and high-glucose stimulation of RPE cells.
• Performed transcriptomic profiling to identify key regulatory proteins.
• Examined the effects of PDZK1 overexpression and senescent cell clearance on DR lesions.

Main Results:

• Upregulated senescence marker p16 in RPE cells of early DR models.
• Downregulated PDZK1 expression in RPE cells under high-glucose conditions.
• PDZK1 overexpression reduced RPE senescence, enhanced cell function, and improved DR lesions in mice.
• Identified a novel PDZK1-14-3-3ε-mTOR pathway regulating RPE senescence.

Conclusions:

• RPE cell senescence is a key factor in DR pathogenesis.
• The PDZK1-14-3-3ε-mTOR axis is a critical regulator of high-glucose-induced RPE senescence.
• Targeting RPE senescence presents a promising therapeutic avenue for DR.