Nitric oxide synthase is the biosynthetic enzyme for the free radical
neurotransmitter nitric oxide. Using an affinity-purified antiserum, n
itric oxide synthase was found to be localized to peripheral ocular ne
rve fibers, related cranial ganglia, and the retina of the rat. In the
eye, nitric oxide synthase-like immunoreactive peripheral nerve fiber
s were visualized mainly in the choroid and about limbal blood vessels
. The anterior uvea was quite sparsely innervated, and the cornea was
negative. Many principal neurons in the pterygopalatine ganglion were
immunoreactive for nitric oxide synthase while very few cells stained
in the superior cervical and trigeminal ganglia. Virtually all nitric
oxide synthase-like immunoreactive pterygopalatine cells were also imm
unostained for vasoactive intestinal polypeptide; nitric oxide synthas
e also partially co-localized with neuropeptide Y in some of the neuro
ns of this ganglion. Pterygopalatine ganglionectomy significantly redu
ced the number of peripheral nitric oxide synthase-like immunoreactive
nerve fibers in the eye. A variety of immunoreactive retinal cells we
re seen. Most cells in the inner nuclear layer or ganglion cell layer
corresponded morphologically to amacrine cells and displaced amacrine
cells. Interplexiform cells and occasional faintly stained cells in th
e outer portion of the inner nuclear layer also were visualized. Nicot
inamide adenine dinucleotide phosphate diaphorase histochemistry gener
ally stained cells of similar distribution but did reveal somewhat mor
e extensive localizations in peripheral ocular tissues, the ciliary ga
nglion, and the retina, compared with nitric oxide synthase immunohist
ochemistry. Nitric oxide synthase thus localizes to peripheral ocular
nerve fibers, chiefly parasympathetic in nature and derived from the p
terygopalatine ganglion, and to several cell types in the retina. Nitr
ic oxide probably acts as a choroidal vasodilator of parasympathetic o
rigin in the eye; the neuropeptide co-localizations in the pterygopala
tine ganglion suggest complex neuromodulatory interactions. The retina
l localizations imply potential neurotransmitter functions for nitric
oxide in this tissue.