ApoM-bound S1P acts via endothelial S1PR1 to suppress choroidal neovascularization and vascular leakage.

ABSTRACT: Neovascular age-related macular degeneration (nAMD) is a major cause of vision loss worldwide. Current standard of care is repetitive intraocular injections of vascular endothelial growth factor (VEGF) inhibitors, although responses may be partial and non-durable. We report that circulating sphingosine 1-phosphate (S1P) carried by apolipoprotein M (ApoM) acts through the endothelial S1P receptor 1 (S1PR1) to suppress choroidal neovascularization (CNV) in mouse laser-induced CNV, modeling nAMD. In humans, low plasma ApoM levels were associated with increased choroidal and retinal pathology. Additionally, endothelial S1pr1 knockout and overexpressing transgenic mice showed increased and reduced CNV lesion size, respectively. Systemic administration of ApoM-Fc, an engineered S1P chaperone pro

SUBMITTER: Jung B 

PROVIDER: S-EPMC12018641 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature