Targeting oxidative stress and inflammation in diabetic retinopathy: the role of PPARs

Abstract:

Diabetic retinopathy (DR) is the leading cause of preventable blindness in working-age adults globally. Current therapies mainly target advanced vascular lesions, leaving early metabolic and inflammatory dysregulation unaddressed. Dysregulated lipid metabolism acts as a critical upstream initiator of DR, converging with oxidative stress and chronic inflammation to form a self-amplifying pathogenic loop driving retinal neurovascular degeneration. Peroxisome proliferator-activated receptors (PPARs) are master transcriptional regulators linking lipid metabolism, oxidative stress, and inflammation. This review systematically delineates the synergistic pathogenic network in DR, comprehensively discusses the pleiotropic retinal protective effects of PPARα and PPARγ, and summarizes the latest advances in PPAR-targeted nano-drug delivery systems that overcome the limitations of traditional agonists. Finally, we highlight key challenges and future directions to advance precision therapy for DR.