2. Academic Validation
  3. Macrophage Sult2b1 promotes pathological neovascularization in age-related macular degeneration

Macrophage Sult2b1 promotes pathological neovascularization in age-related macular degeneration

  • Life Sci Alliance. 2023 Aug 7;6(11):e202302020. doi: 10.26508/lsa.202302020.
Yafang Wang 1,  Yang Liu 1,  Yan Wang 2,  Yidong Wu 1,  Zhixuan Chen 1,  Feng Wang 3,  Xiaoling Wan 4 5,  Fenghua Wang 6 5 7 8 9,  Xiaodong Sun 1 5 7 8 9
Affiliations

Affiliations

  • 1 Department of Ophthalmology, Shanghai General Hospital (Shanghai First People's Hospital), Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 2 Medical Research Center, Peking University Third Hospital, Beijing, China.
  • 3 Shanghai Institute of Immunology, Department of Immunology and Microbiology, State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University School of Medicine, Shanghai, China wangfeng16@sjtu.edu.cn.
  • 4 Department of Ophthalmology, Shanghai General Hospital (Shanghai First People's Hospital), Shanghai Jiao Tong University School of Medicine, Shanghai, China shaolin.72@163.com.
  • 5 Shanghai Key Laboratory of Ocular Fundus Diseases, Shanghai, China.
  • 6 Department of Ophthalmology, Shanghai General Hospital (Shanghai First People's Hospital), Shanghai Jiao Tong University School of Medicine, Shanghai, China shretina@sjtu.edu.cn.
  • 7 Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China.
  • 8 National Clinical Research Center for Eye Diseases, Shanghai, China.
  • 9 Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai, China.
PMID: 37550000 DOI: 10.26508/lsa.202302020
Abstract

Disordered immune responses and Cholesterol metabolism have been implicated in age-related macular degeneration (AMD), the leading cause of blindness in elderly individuals. SULT2B1, the key Enzyme of sterol sulfonation, plays important roles in inflammation and Cholesterol metabolism. However, the role and underlying mechanism of SULT2B1 in AMD have not been investigated thus far. Here, we report that SULT2B1 is specifically expressed in macrophages in choroidal neovascularization lesions. Sutl2b1 deficiency significantly reduced leakage areas and inhibited pathological angiogenesis by inhibiting M2 macrophage activation in vivo and in vitro. Mechanistically, loss of Sult2b1 activated LXRs and subsequently increased ABCA1 and ABCG1 (ABCA1/G1)-mediated Cholesterol efflux from M2 macrophages. LXR inhibition (GSK2033 treatment) in Sult2b1 -/- macrophages reversed M2 polarization and decreased intracellular Cholesterol capacity to promote pathological angiogenesis. In contrast to SULT2B1, STS, an Enzyme of sterol desulfonation, protected against choroidal neovascularization development by activating LXR-ABCA1/G1 signalling to block M2 polarization. Collectively, these data reveal a Cholesterol metabolism axis related to macrophage polarization in neovascular AMD.

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