Alterations of ocular nitric oxide synthase in human glaucoma.
OBJECTIVE
The authors recently reported that sites of outflow resistance and regulation in the human eye are highly enriched in the endothelial isoform of nitric oxide (NO) synthase (ecNOS). In vasculature, ecNOS activation is associated with altered vascular resistance and, in the stomach, defects in NO are associated with pathologic gastric hypertension. Because human glaucoma sometimes is associated with an increase in intraocular pressure and resistance changes in the aqueous outflow pathway (OP), the authors have investigated the possibility that alterations in NO or defects in NO-synthesizing tissues might exist in glaucomatous eyes.


METHODS
Occurrence, distribution, and extent of sites of ocular NO production in the anterior segments of 16 normal eyes (10 patients) and 17 eyes (12 patients) with a history of primary open-angle glaucoma (POAG) were determined using the NO-indicator marker, NADPH-diaphorase (NADPH-d), which is known to colocalize with ecNOS immunoreactivity. Analysis of NADPH-d reactivity in tissues was combined with examination of overall cell distribution and use of neuron-specific markers.


RESULTS
The ciliary muscle (CM) and OP of glaucomatous eyes showed marked differences in the amount and distribution of NADPH-d and alterations in gross structure. NADPH-d reactivity was decreased in trabecular meshwork (TM) and Schlemm's canal, and there was a marked reduction of anterior longitudinal CM fibers that insert near (and may normally regulate resistance in) the TM.


CONCLUSIONS
Abnormalities in NO or NO-containing cells occur in POAG. These abnormalities may be causally related to glaucoma or may be a manifestation of the disease or its treatment. In either case, such alterations, together with recent pharmacologic studies showing that NO-mimicking nitrovasodilators alter IOP, indicate that NO has relevance to the course, treatment, or both, or some forms of this disease.
Nathanson
J A
JA
Department of Neurology, Harvard Medical School, Massachusetts, USA.
McKee
M
M
D000368:Aged; D000369:Aged, 80 and over; D000594:Amino Acid Oxidoreductases / Q000378:metabolism*; D000869:Anterior Eye Segment / Q000201:enzymology; D000911:Antibodies, Monoclonal; D002924:Ciliary Body / Q000201:enzymology / Q000473:pathology; D005260:Female; D005902:Glaucoma, Open-Angle / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009132:Muscles / Q000201:enzymology / Q000473:pathology; D009252:NADPH Dehydrogenase / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D019001:Nitric Oxide Synthase; D014129:Trabecular Meshwork / Q000201:enzymology / Q000473:pathology
D000911:Antibodies, Monoclonal; D009419:Nerve Tissue Proteins; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D009252:NADPH Dehydrogenase