Oxidants, nitric oxide and prostanoids in the developing ocular vasculature: a basis for ischemic retinopathy

The choroid is the main source of oxygen to the retina In contrast to the a dult, the absence of autoregulation of choroidal blood flow in the newborn leads to hyperoxygenation of the retina. In the immature retina which conta ins relatively low levels of antioxidants this hyperoxygenation favors pero xidation including the generation of biologically active isoprostanes, and results in vasoconstriction and vascular cytotoxicity leading to ischemia, which predisposes to the development of a vasoproliferative retinopathy, co mmonly termed retinopathy of prematurity. During frequently encountered oxi dative stress to the perinate, the combined absence of vascular autoregulat ion and excessive oxygen delivery to the eyes of the developing subject is largely the result of a complex epigenetic and genetic interplay between pr ostanoids and nitric oxide (NO) systems on vasomotor regulation. The effect s of certain prostaglandins are NO-dependent; conversely, those of NO have also been found to be largely prostaglandin I-2-mediated in the eye; and NO synthase expression seems to be significantly regulated by other prostagla ndins apparently through activation of functional perinuclear prostanoid re ceptors which affect gene transcription. The increased production of both p rostaglandins and NO in the perinate augment ocular blood flow and as a res ult oxygen delivery to an immature retina partly devoid of antioxidant defe nses. The ensuing peroxidation results in impaired circulation (partly thro mboxane A(2)-dependent) and vascular integrity, leading to ischemia which p redisposes to abnormal preretinal neovascularization, a major feature of is chemic retinopathy. Because tissue oxygenation is largely dependent upon ci rculation and critical in the generation of reactive oxygen species, and si nce the latter exert a major contribution in the pathogenesis of retinopath y of prematurity, it is important to understand the mechanisms that govern ocular blood flow. In this review we focus on the important and complex int eraction between prostanoid, NO and peroxidation products on circulatory co ntrol of the immature retina. (C) 2000 Elsevier Science B.V. All rights res erved.