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Shakeel Shareef, Akira Sawada, Arthur H. Neufeld; Isoforms of Nitric Oxide Synthase in the Optic Nerves of Rat Eyes with Chronic Moderately Elevated Intraocular Pressure. Invest. Ophthalmol. Vis. Sci. 1999;40(12):2884-2891.
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purpose. To investigate the hypothesis that nitric oxide (NO) in the optic nerve
heads of rats with chronic moderately elevated intraocular pressure
(IOP) contributes to neurotoxicity of the retinal ganglion cells, the
presence of the three isoforms of nitric oxide synthase (NOS) was
determined in the tissue.
methods. Unilateral chronic moderately elevated IOP was produced in rats by
cautery of three episcleral vessels. Histologic sections of optic
nerves from eyes with normal IOP and with chronic moderately elevated
IOP were studied by immunohistochemistry and by immunoblot analysis.
Polyclonal antibodies to NOS-1, NOS-2, NOS-3, and glial fibrillary
acidic protein (GFAP) were localized with immunoperoxidase.
results. In the optic nerve of rat eyes with normal IOP, NOS-1 was
constitutively present in astrocytes, pericytes and nerve terminals in
the walls of the central artery. NOS-2 was not present in eyes with
normal IOP. In these eyes, NOS-3 was constitutively present in the
vascular endothelia of large and small vessels. Rat eyes treated with
three-vessel cautery had sustained elevated IOP (1.6 fold) for at least
3 months. In these eyes, no obvious changes in NOS-1 or NOS-3 were
noted. However, at time points as early as 4 days of chronic moderately
elevated IOP, NOS-2 appeared in astrocytes in the optic nerve heads of
these eyes and persisted for up to 3 months. Immunoblot analysis did
not detect differences in NOS isoforms.
conclusions. The cellular distributions of constitutive NOS isoforms in the rat
optic nerve suggest physiological roles for NO in this tissue. NOS-1 in
astrocytes may produce NO as a mediator between neighboring cells. NO,
produced by NOS-1 in pericytes and nitrergic nerve terminals and by
NOS-3 in vascular endothelia, is probably a physiological vasodilator
in this tissue. In eyes with chronic moderately elevated IOP, NOS-2 is
apparently induced in astrocytes. The excessive NO production that is
associated with this isoform may contribute to the neurotoxicity of the
retinal ganglion cells in eyes with chronic moderately elevated
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