Sphingosine-1-phosphate receptor 2 inhibition ameliorates familial exudative vitreoretinopathy models.

ABSTRACT: Familial exudative vitreoretinopathy (FEVR) is an inherited childhood blinding disorder with close to 85% of molecularly determined cases due to rare variants in the genes encoding members of the frizzled 4 (FZD4) receptor complex. FEVR causes blindness due to complications arising from developmental peripheral non-perfusion of the retina. We sought to find a small molecule that could ameliorate FEVR models. In this study, we determine that the sphingosine1-phosphate receptor 2 (S1PR2) antagonist JTE-013 can ameliorate cellular and mouse models of FEVR. Using human primary retinal microvascular endothelial cells (hRMECs), we show that either knockdown of FZD4 expression using shRNA or expression of a known FEVR-causing dominant negative allele of FZD4 decreases the ability of hRMECs to tub

SUBMITTER: Feridooni HA 

PROVIDER: S-EPMC12830201 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature