Regulation of intracellular heme by FLVCR2 modulates retinal angiogenesis

Fowler syndrome is an embryonic lethal disease with proliferative vasculopathy and hydranencephaly-hydrocephaly of the central nervous system due to mutations in Feline Leukemia Virus Subgroup C Receptor-Related Protein 2 (FLVCR2) characterized by large regions of hypovascularization along with glomeruloid formation of poorly organized vascular endothelial cell mass. Recent animal models have characterized reduced vascularization in brain in gene deletion models of Flvcr2.

Here, we use conditional knockout of Flvcr2 in mice and knockdown in cell culture to explore retinal development and further understand the mechanism of angiogenic regulation by Flvcr2. Gene deletion of Flvcr2 or chemical inhibition of heme synthesis led to reduced retinal vascular expansion and reduced formation of deep capillary plexus with a partial penetrance of a severe phenotype with dramatic reduction in vascular expansion and glomeruloid and endothelial mass formation.