Microglial Polarization in Retinal Neovascularization: Friend or foe?

Current anti-vascular endothelial growth factor (VEGF) therapies are constrained by treatment resistance and the burden of frequent injections, highlighting an urgent need to uncover novel regulatory mechanisms. As the resident immune cells of the retina, microglia play a critical and complex role in RNV through their functional polarization.

Most studies indicate that pro‑inflammatory M1‑type polarization aggravates vascular leakage and pathological vessel formation by releasing factors including VEGF, Tumor Necrosis Factor-alpha (TNF‑α), and Interleukin-1 beta (IL‑1β), whereas the repair‑oriented M2‑type polarization is associated with promoting vascular repair and maintaining homeostasis. However, emerging technologies such as single‑cell transcriptomics have revealed that microglia exhibit considerable phenotypic heterogeneity within the RNV microenvironment, extending beyond the classical M1/M2 dichotomy.