Autophagy and mitophagy in diabetic retinopathy: The effects and mechanism of action on the neurovascular unit

While diabetic retinopathy (DR) is the primary cause of vision impairment and blindness in people with diabetes, current treatments fail to target early pathogenic mechanisms to halt disease progression. The development of DR involves complex cellular stress responses associated with metabolic dysregulation. Recent studies have highlighted the critical functions of autophagy, particularly mitophagy, in DR and how it contributes to the malfunction of the retinal neurovascular unit (NVU) and disease progression. Emerging insights have elucidated the interplay between autophagy, ER stress, and regulatory genes such as DRAM2, with pivotal roles for mitophagy-related pathways, including PINK1/Parkin and BNIP3/NIX-FUNDC1. This review systematically organizes and analyzes recent advances in research on how autophagy and mitophagy regulate ER stress, mitochondrial homeostasis, and the function of diverse NVU cell types. We present evidence that dysregulation of these processes compromises NVU integrity and accelerates DR progression. By clarifying the molecular links between autophagy, mitophagy, and NVU dysfunction, this review offers new insights for developing precision interventions and innovative therapies for early intervention of DR.