Investigative Ophthalmology & Visual Science, Vol 36, 1765-1773, Copyright © 1995 by Association for Research in Vision and Ophthalmology

ARTICLES AND REPORTS

Identification of an extensive system of nitric oxide-producing cells in the ciliary muscle and outflow pathway of the human eye

JA Nathanson and M McKee
Department of Neurology, Harvard Medical School, Massachusetts, USA.

PURPOSE. Nitric oxide (NO) is an important intracellular and intercellular regulator in nerve tissue as well as in vascular endothelium, smooth muscle, and certain other cell types. In the ocular anterior segment, studies in rat have revealed a comparatively restricted distribution of the NO synthetic enzyme, NO synthase (NOS- 1). Recent physiological studies, however, have shown that NO-mimicking nitrovasodilators can alter intraocular pressure in monkeys through an action (at least in part) on outflow resistance. The current studies, which determine the sites of NO synthesis in the human outflow pathway, were performed to provide an anatomic and biochemical explanation for these observations. METHODS. The occurrence and distribution of sites of ocular NO production in postmortem human eyes were determined using the isozyme-independent NO-indicator marker, NADPH-diaphorase (NADPH- d), together with direct biochemical assay and immunocytochemical localization of specific NO synthase (NOS) isoforms. RESULTS. The ciliary muscle (CM) and outflow pathway of normal human eyes were found to be substantially enriched in NADPH-d, the majority of which, by immunological analysis, consisted not of NOS-1 (brain or bNOS) but rather of NOS type 3 (endothelial cell or ecNOS). Biochemical analysis confirmed the NADPH-dependent production of NO and, unlike the primarily soluble distribution of bNOS, activity was found in both particulate and soluble fractions. NO reactivity was enriched in major sites of outflow resistance (trabecular meshwork and Schlemm's canal) as well as in collecting channels and was particularly prominent in the CM, especially in the anatomically distinct longitudinal subgroup of CM fibers that insert near (and may normally play a role in regulating resistance in) the trabecular meshwork. CONCLUSION. The human outflow pathway and CM are enriched sites of NO synthesis. These sites are anatomically distributed in such a manner as to suggest that one possible role for NO in the anterior segment may be to modulate outflow resistance either directly at the level of the trabecular meshwork, Schlemm's canal and collecting channels, or indirectly through alteration in the tone of the longitudinal CM.

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