Neurovascular unit-targeted therapeutic strategies in diabetic retinopathy

Diabetic retinopathy (DR) has traditionally been regarded as a microvascular complication, but increasing evidence supports its classification as a neurovascular disease. The retinal neurovascular unit (NVU), comprising neurons, glial, and vascular, elements, is crucial for retinal homeostasis and is disrupted early in DR. The present narrative review aims to summarize current clinical evidence on the role of NVU dysfunction in DR and to evaluate the clinical benefits of NVU-oriented therapeutic strategies. Clinical data indicate that neurodegeneration and glial activation, precede overt blood-retinal barrier damage and microvascular breakdown observable in DR. Emerging NVU-oriented treatments, including topical neuroprotective agents, anti-inflammatory therapies, and selected systemic metabolic drugs, show beneficial effects on functional and structural retinal outcomes. Targeting NVU may represent a disease-modifying strategy, enabling earlier intervention and potentially preventing irreversible vision loss in DR. Further well-designed prospective and randomized studies are warranted to strengthen the level of evidence and validate this therapeutic approach.