Here, we show that suppressed NO formation via the use of the competitive NOS inhibitor, Nω-Methyl-l-arginine (L-NMMA), which inhibits NO formation from all three NOS variants (eNOS, inducible NOS, and neuronal NOS), or an eNOS mutant, S1176A, negates neovascular tuft formation and vascular leakage during retinal disease. Here, NOS2 is linked to Abnormal retinal morphology.