NITRIC-OXIDE SYNTHASE IN THE HUMAN GLAUCOMATOUS OPTIC-NERVE HEAD

Objectives: To investigate the hypothesis that nitric oxide contribute s to neurotoxicity in the optic nerve heads of patients with primary o pen-angle glaucoma, we have determined the presence of the 3 isoforms of nitric oxide synthase (NOS) in the tissue. Methods: Histological se ctions of optic nerve heads from normal subjects and patients with gla ucoma who have moderate to advanced nerve damage were studied by immun ohistochemistry. Polyclonal antibodies to NOS-1, NOS-2, and NOS-3 were localized with immunoperoxidase staining. Results: In normal eyes, NO S-1 is sparsely present in astrocytes throughout the optic nerve head. In glaucomatous optic nerve heads, almost every astrocyte is positive for NOS-1. Nitric oxide synthase-1 immunoreactivity is abundantly pre sent throughout the prelaminar region and the lamina cribrosa and is l ocalized inside the diminished nerve fiber bundles. Nitric oxide synth ase-2 is present in a few cells in the disorganized lamina cribrosa of the glaucomatous eye and is not present at all in normal tissue. Nitr ic oxide synthase-3 is present in normal eyes in the vascular endothel ia of small blood vessels of the prelaminar region. In glaucomatous ti ssue, NOS-3 is present in astrocytes and in the vascular endothelia of large and small vessels. Conclusions: The 3 isoforms of NOS are prese nt in apparently increased amounts in the optic nerve head of patients with primary open-angle glaucoma. The increased presence of NOS-1 and the induction of NOS-2 in astrocytes of the lamina cribrosa suggest t hat the glaucomatous optic nerve head is exposed to excessive levels o f nitric oxide, which may be neurodestructive, locally, to the axons o f the retinal ganglion cells. Conversely, the increased presence of NO S-3 in vascular endothelia may be neuroprotective by causing vasodilat ion and increased blood flow in the tissue.