Interferon-mediated regulation of the neurovascular unit in diabetic retinopathy

Diabetic retinopathy (DR) is an important complication of diabetes mellitus (DM) and one of the leading causes of preventable blindness. The onset and progression of DR involve multiple molecular mechanisms, among which inflammatory responses and immune dysregulation play important roles. Interferons (IFNs), as key mediators of the immune system, exhibit complex regulatory effects during the progression of DR. Type I IFNs generally exert protective effects by suppressing inflammation, inhibiting pathological angiogenesis, and maintaining endothelial barrier integrity; however, certain IFN-α subtypes may also induce the production of pro-inflammatory factors. In contrast, type II IFN can promote inflammatory responses, induce apoptosis, and facilitate aberrant angiogenesis, while under specific conditions it may also inhibit abnormal cell proliferation. IFNs regulate multiple cell types within the retinal neurovascular unit (NVU) through diverse signaling pathways, thereby affecting blood-retinal barrier (BRB) homeostasis, neurodegeneration, and neovascularization.

IFNs exert both protective and detrimental effects in DR. Elucidating the differential regulatory roles of IFNs across various cell types and their functional changes at different stages of disease progression may facilitate precise modulation of the retinal microenvironment and provide a theoretical basis for personalized treatment of DR.