Nitric Oxide: A Review of Its Role in Retinal Function and Disease

Abstract

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.

Sildenafil citrate on retrobulbar and retinal circulation of rabbits

“…The increase can be attributed to the dilation of retinal arterial vessels, by increased release of nitric oxide, through PDE5 inhibition (WRIGHT, 2006). Blood vessels are innervated by nitric oxide-producing neurons, which play an important role in local regulation of ocular blood fl ow, through the autonomic nervous system (GOLDSTEIN et al, 1996;TODA & NAKANISHI-TODA, 2007).…”

Functional Properties of Neuroglobin and Cytoglobin. Insights into the Ancestral Physiological Roles of Globins

“…Ca 2+ -dependent, neuronal NOS is moreover present in several parts of the retina, including photoreceptors (33,34), and in Purkinje cells (35). Given the high affinity of globins (36), including Ngb (37) for NO, one would expect Ngb to be in the Fe 2+ 7NO form inside NO-producing neurons.…”

Expression of the cystine-glutamate exchanger (xc −) in retinal ganglion cells and regulation by nitric oxide and oxidative stress

“…Recently, we and others have reported that they die in diabetic retinopathy [20][21][22]. Nitric oxide (NO) is a molecule implicated in the pathogenic complications of diabetic retinopathy [23][24][25]. Yilmaz and coworkers [26] reported a fivefold elevation of NO in the vitreous of patients with proliferative diabetic retinopathy compared with nondiabetic control patients.…”

“…Yilmaz and coworkers [26] reported a fivefold elevation of NO in the vitreous of patients with proliferative diabetic retinopathy compared with nondiabetic control patients. Given that NO levels are increased in diabetic retinopathy [23][24][25][26], coupled with our findings that NO can upregulate system x c -transporter in RPE cells [4], we asked whether this transporter is present in ganglion cells and if so, whether it is upregulated by NO in these cells.…”