Nitric Oxide Synthase in the Human Glaucomatous Optic Nerve Head

TLDR

The study aimed to test whether nitric oxide contributes to neurotoxicity in primary open‑angle glaucoma by mapping the three nitric oxide synthase isoforms in optic nerve head tissue. Immunohistochemical staining with polyclonal antibodies against NOS‑1, NOS‑2, and NOS‑3 was performed on histological sections from normal and glaucomatous optic nerve heads. Glaucomatous optic nerve heads showed markedly increased NOS‑1 in astrocytes, sporadic NOS‑2 in lamina cribrosa cells, and NOS‑3 in both astrocytes and vascular endothelia, suggesting excess nitric oxide may be neurodestructive while NOS‑3‑mediated vasodilation could be neuroprotective.

Abstract

To investigate the hypothesis that nitric oxide contributes to neurotoxicity in the optic nerve heads of patients with primary open-angle glaucoma, we have determined the presence of the 3 isoforms of nitric oxide synthase (NOS) in the tissue.Histological sections of optic nerve heads from normal subjects and patients with glaucoma who have moderate to advanced nerve damage were studied by immunohistochemistry. Polyclonal antibodies to NOS-1, NOS-2, and NOS-3 were localized with immunoperoxidase staining.In normal eyes, NOS-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 present throughout the prelaminar region and the lamina cribrosa and is localized inside the diminished nerve fiber bundles. Nitric oxide synthase-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. Nitric oxide synthase-3 is present in normal eyes in the vascular endothelia of small blood vessels of the prelaminar region. In glaucomatous tissue, NOS-3 is present in astrocytes and in the vascular endothelia of large and small vessels.The 3 isoforms of NOS are present 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 that the glaucomatous optic nerve head is exposed to excessive levels of nitric oxide, which may be neurodestructive, locally, to the axons of the retinal ganglion cells. Conversely, the increased presence of NOS-3 in vascular endothelia may be neuroprotective by causing vasodilation and increased blood flow in the tissue.