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

Neovascular age-related macular degeneration (nAMD) is a major cause of vision loss in the elderly. Vascular endothelial growth factor (VEGF) inhibitors, which are approved for the treatment of nAMD, require repetitive intraocular injections and suffer from partial and non-durable treatment response. We report here 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 laser-induced mouse nAMD model. Low plasma ApoM increased whereas high plasma ApoM reduced laser-induced CNV. In addition, endothelial S1pr1 knockout and overexpressing transgenic mice showed larger and reduced CNV lesion size, respectively. Systemic administration of ApoM-Fc, an engineered S1P chaperone protein, not only attenuated CNV to an equivalent degree as anti-VEGF antibody treatment but also suppressed vascular permeability. We suggest that the circulating ApoM-bound S1P action on en..., , , # ApoM-bound S1P acts via endothelial S1PR1 to suppress choroidal neovascularization and vascular leak

Dataset DOI: [10.5061/dryad.z8w9ghxpp](10.5061/dryad.z8w9ghxpp)

## Description of the data and file structure

Neovascular age-related macular degeneration (nAMD) is a major cause of vision loss in the elderly. We investigated the role of Shingosine 1-phosphate (S1P) signaling via endothelial S1PR1 action in nAMD. Laser-induced choroidal neovascularization (CNV) mouse model which mimics human nAMD was employed on genetic mouse models that modulate *S1pr1* gene in endothelium (*S1pr1* ECKO and *S1pr1* ECTG) as well as  *Apom* gene (*Apom* KO and *Apom* TG). Two delivery routes of ApoM-Fc, an engineered S1P chaperone protein, were tested to determine pharmacokinetics and plasma S1P levels in vivo. ApoM-Fc administration alone or in combination with anti-VEGF treatment were examined in mice after laser photocoagulation. Mouse RPE/ Choroid flat mount was prepared 10 to 14 days post-laser...,