Mechanisms of action of retinal microglia in diabetic retinopathy (Review).

Diabetic retinopathy (DR), a leading cause of blindness in diabetic microvascular complications, is pathologically associated with the dynamic regulation of retinal microglia. The present review systematically elucidated the dual roles of microglia in DR pathogenesis. Under physiological conditions, microglia maintain blood‑retinal barrier (BRB) integrity by phagocytosing metabolic debris and secreting neurotrophic factors. However, hyperglycaemic stress induces pathological M1 polarization, triggering a cytokine storm (TNF‑α and IL‑1β) via the Toll‑like receptor 4/myeloid differentiation primary response 88/NF‑κB signalling axis, which synergizes with proangiogenic factors (such as VEGF and insulin‑like growth factor 1) to exacerbate BRB breakdown and pathological neovascularization. Notably, activated microglia amplify inflammatory cascades through astrocyte‑Müller cell interaction networks, accelerating neurovascular unit dysfunction. Emerging therapeutic strategies targeting microglial polarization homeostasis (such as promoting M2 anti‑inflammatory phenotypic shifts) and blocking critical inflammatory signalling pathways present novel opportunities for developing multitarget therapeutic agents with combined neuroprotective and anti‑vasopermeability properties. By elucidating microglial heterogeneity and intercellular regulatory networks, the present review highlighted the importance of precise modulation of immune homeostasis in DR management, providing a theoretical foundation for overcoming the limitations of single‑target therapies.