A specific RIP3⁺ subpopulation of microglia promotes retinopathy through a hypoxia-triggered necroptotic mechanism.

ABSTRACT: Retinal neovascularization is a leading cause of severe visual loss in humans, and molecular mechanisms of microglial activation-driven angiogenesis remain unknown. Using single-cell RNA sequencing, we identified a subpopulation of microglia named sMG2, which highly expressed necroptosis-related genes Rip3 and Mlkl. Genetic and pharmacological loss of function demonstrated that hypoxia-induced microglial activation committed to necroptosis through the RIP1/RIP3-mediated pathway. Specific deletion of Rip3 gene in microglia markedly decreased retinal neovascularization. Furthermore, hypoxia induced explosive release of abundant FGF2 in microglia through RIP3-mediated necroptosis. Importantly, blocking signaling components of the microglia necropotosis-FGF2 axis largely ablated retinal angiog

SUBMITTER: He C 

PROVIDER: S-EPMC7980367 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature