Diabetic retinopathy is the most common microvascular complication of diabetes,
characterized by the formation of fibrovascular membranes that consist of a variety of cells
including vascular endothelial cells (ECs). New therapeutic approaches for this diabetic
complication are urgently needed. Here, we report that in cultured human retinal
microvascular (HRECs) high glucose induced expression of p110, which was also
expressed in ECs of fibrovascular membranes from diabetic patients. This catalytic subunit
of a receptor regulated PI3K isoform is known to be highly-enriched in leukocytes. Using
genetic and pharmacological approaches, we show that p110 activity in cultured ECs
controls Akt activation, cell proliferation, migration, and tube formation induced by
vascular endothelial growth factor, basic fibroblast growth factor, and epidermal growth
factor. Using a mouse model of oxygen-induced retinopathy, p110 inactivation was found
to attenuate pathological retinal angiogenesis. p110 inhibitors have been approved for use
in human B-cell malignancies. Our data suggest that antagonizing p110 constitutes a
previously-unappreciated therapeutic opportunity for diabetic retinopathy
