Previously shown to be protective against hyperoxia-induced vessel loss in OIR, erythropoietin has also been shown to increase BH4 bioavailability and protect against oxidative stress induced by eNOS uncoupling in the cerebral microvasculature, suggesting a BH4-eNOS–mediated mechanism for its beneficial effects on the retina.43,44 Several other agents, notably ascorbic acid and folate, are also known to alter EC-BH4 levels and could therefore be administered safely to premature infants to prevent ROP. Here, NOS3 is linked to retinopathy of prematurity.