Using a pharmacologic inhibitor of HIF-2, PT2385 (22), which has shown promise for the treatment of patients with renal cell carcinoma (23, 24), we demonstrate that preventing HIF-2–dependent PAI-1 expression in retinal vascular cells prevents the development of retinal NV in OIR mice. This evidence concerns the gene SERPINE1 and hereditary clear cell renal cell carcinoma.