%0 Journal Article
%T Autophagy-mediated activation of the AIM2 inflammasome enhances M1 polarization of microglia and exacerbates retinal neovascularization.
%A Liu X
%A Zhou Q
%A Meng J
%A Zuo H
%A Li R
%A Zhang R
%A Lu H
%A Zhang Z
%A Li H
%A Zeng S
%A Tian M
%A Wang H
%A Hu K
%A Li N
%A Mao L
%A Hou S
%J MedComm (2020)
%V 5
%N 8
%D 2024 Aug
%M 39081514
暂无%R 10.1002/mco2.668
%X Retinopathy of prematurity (ROP) is a retinal neovascularization (RNV) disease that is characterized by abnormal blood vessel development in the retina. Importantly, the etiology of ROP remains understudied. We re-analyzed previously published single-cell data and discovered a strong correlation between microglia and RNV diseases, particularly ROP. Subsequently, we found that reactive oxygen species reduced autophagy-dependent protein degradation of absent in melanoma 2 (AIM2) in hypoxic BV2 cells, leading to increased AIM2 protein accumulation. Furthermore, we engineered AIM2 knockout mice and observed that the RNV was significantly reduced compared to wild-type mice. In vitro vascular function assays also demonstrated diminished angiogenic capabilities following AIM2 knockdown in hypoxic BV2 cells. Mechanistically, AIM2 enhanced the M1-type polarization of microglia via the ASC/CASP1/IL-1β pathway, resulting in RNV. Notably, the administration of recombinant protein IL-1β exacerbated angiogenesis, while its inhibition ameliorated the condition. Taken together, our study provides a novel therapeutic target for ROP and offers insight into the interaction between pyroptosis and autophagy.