2. Academic Validation
  3. Autophagy-mediated activation of the AIM2 inflammasome enhances M1 polarization of microglia and exacerbates retinal neovascularization

Autophagy-mediated activation of the AIM2 inflammasome enhances M1 polarization of microglia and exacerbates retinal neovascularization

  • MedComm (2020). 2024 Jul 29;5(8):e668. doi: 10.1002/mco2.668.
Xianyang Liu 1 2,  Qian Zhou 1 2,  Jiayu Meng 3,  Hangjia Zuo 1 2,  Ruonan Li 1 2,  Rui Zhang 4,  Huiping Lu 1 2,  Zhi Zhang 1 2,  Hongshun Li 1 2,  Shuhao Zeng 1 2,  Meng Tian 5,  Hong Wang 5,  Ke Hu 1 2,  Na Li 6,  Liming Mao 7,  Shengping Hou 1 5
Affiliations

Affiliations

  • 1 The First Affiliated Hospital of Chongqing Medical University Chongqing China.
  • 2 Chongqing Key Laboratory of Ophthalmology Chongqing China.
  • 3 Sichuan Provincial Key Laboratory for Human Disease Gene Study Sichuan Provincial People's Hospital University of Electronic Science and Technology of China Chengdu China.
  • 4 Department of Ophthalmology Qilu Hospital Cheeloo College of Medicine Shandong University Jinan China.
  • 5 Beijing Institute of Ophthalmology Beijing Tongren Eye Center Beijing Ophthalmology & Visual Sciences Key Laboratory Beijing Tongren Hospital Capital Medical University Beijing China.
  • 6 Department of Laboratory Medicine, Beijing Tongren Hospital Capital Medical University Beijing China.
  • 7 Department of Immunology School of Medicine Nantong University Nantong China.
PMID: 39081514 DOI: 10.1002/mco2.668
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.

Keywords

AIM2 inflammasomes; autophagy; microglia; retinal angiogenesis; retinopathy of prematurity.

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