Targeting Retinal Neuroglial Vascular Unit Damage: Novel Therapeutic Strategies for Early-Stage Diabetic Retinopathy.

Diabetic retinopathy (DR) is a prevalent chronic ocular complication of diabetes, which ranks as the leading cause of blindness in individuals aged 40 and above. Recent studies have demonstrated that neuroglial vascular unit (NGVU) injury leads to distinct fundus changes in DR, including exudates, cotton-fluff spots, microangiomas, hemorrhages, and neovascularization. Currently, the primary clinical treatment options primarily target retinal microvascular degeneration during the middle and late stages of DR through techniques such as retinal laser photocoagulation, antivascular endothelial growth factor (VEGF) therapy, and vitrectomy. However, progression to these stages often results in irreversible damage to visual acuity with limited treatment efficacy. In recent years, relevant research has confirmed that NGVU injury occurs prior to retinal microangiopathy in patients with DR, and it is closely associated with impaired visual function. Therefore, targeting NGVU holds potential for future therapeutic interventions aimed at preventing and treating early-stage DR. This review identifies six key molecular targets (P2X7 receptor, NLRP3 inflammasome, retinal microglial cell necroptosis pathway, spermine oxidase, and AQP4-AS1 lncRNA) that mitigate NGVU dysfunction in preclinical models. Literature search was conducted in PubMed/Embase using keywords "diabetic retinopathy," "neuroglial vascular unit," and "targeted therapy" (2018-2024), focusing on preclinical studies with in vivo efficacy data.