MacrophageSult2b1promotes pathological neovascularization in age-related macular degeneration

• DOI: 10.26508/lsa.202302020
• Publication Date: 2023-08-09T15:52:50Z
• Authors: Yafang Wang; Yang Liu; Yan Wang; Yidong Wu; Zhixuan Chen; Feng Wang; Xiaoling Wan; Fenghua Wang; Xiaodong Sun
• Keywords: ABCG1; Macrophage polarization; Liver X receptor; Oxysterol

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