PDF(Pubmed)
Abstract：
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.
摘要：
早产儿视网膜病(ROP)是一种视网膜新生血管(RNV)疾病,其特征在于视网膜中血管发育异常。重要的是,ROP的病因仍未得到充分研究。我们重新分析了以前发表的单细胞数据，发现小胶质细胞和RNV疾病之间存在很强的相关性，尤其是ROP。随后，我们发现活性氧减少了缺氧BV2细胞中黑素瘤2（AIM2）中缺失的自噬依赖性蛋白降解，导致AIM2蛋白积累增加。此外，我们改造了AIM2敲除小鼠,观察到与野生型小鼠相比RNV显著降低。体外血管功能测定也证明在低氧BV2细胞中AIM2敲低后血管生成能力降低。机械上,AIM2通过ASC/CASP1/IL-1β途径增强小胶质细胞的M1型极化,导致RNV。值得注意的是,重组蛋白IL-1β的施用会加剧血管生成，而它的抑制作用改善了病情。一起来看,我们的研究为ROP提供了一个新的治疗靶点,并提供了对焦凋亡和自噬之间相互作用的见解.
