Nitric oxide: a review of its role in retinal function and disease.

Nitric oxide synthase (NOS), the enzyme that catalyzes the formation of nitric oxide from L-arginine, exists in three major isoforms, neuronal, endothelial, and immunologic. Neuronal and endothelial isoforms are constitutively expressed, and require calcium for activation. Both of these isoforms can be induced (i.e., new protein synthesis occurs) under appropriate conditions. The immunologic isoform is not constitutively expressed, and requires induction usually by immunologic activation; calcium is not necessary for its activation. Neuronal and immunologic NOS have been detected in the retina. Neuronal NOS may be responsible for producing nitric oxide in photoreceptors and bipolar cells. Nitric oxide stimulates guanylate cyclase of photoreceptor rod cells and increases calcium channel currents. In the retina of cats, NOS inhibition impairs phototransduction as assessed by the electroretinogram. Inducible nitric oxide synthase, found in Müller cells and in retinal pigment epithelium, may be involved in normal phagocytosis of the retinal outer segment, in infectious and ischemic processes, and in the pathogenesis of diabetic retinopathy. Nitric oxide contributes to basal tone in the retinal circulation. To date, findings are conflicting with respect to its role in retinal autoregulation. During glucose and oxygen deprivation, nitric oxide may increase blood flow and prevent platelet aggregation, but it may also mediate the toxic effects of excitatory amino acid release. This reactive, short-lived gas is involved in diverse processes within the retina, and its significance continues to be actively studied.