NITRIC-OXIDE MODULATES CGMP LEVELS IN NEURONS OF THE INNER AND OUTER RETINA IN OPPOSITE WAYS

In the mammalian retina, neuronal nitric oxide synthase (NOS) is mainl y localized in subpopulations of amacrine cells. One function of nitri c oxide (NO) is to stimulate soluble guanylate cyclases which in rum s ynthesize cGMP. We used an antibody specific for cGMP to demonstrate c GMP-like immunoreactivity (cG-IR) in bovine, rat, and rabbit retinae a nd investigated the effects on cCMP levels of both exogenously applied NO and of endogenously released WO. We found that cGMP levels in inne r and outer retina were controlled in opposite ways. In the presence o f the NO-donors SNP, SIN-1 or SNAP, cG-IR was prominent in neurons of the inner retina, mainly in cone bipolar cells, some amacrine and gang lion cells. Retinae incubated in IBMX showed weak cG-IR in bipolar cel ls. Glutamate increased cG-IR in the inner retina, presumably by stimu lating endogenous NO release, whereas NOS inhibitors or GABA and glyci ne decreased cG-IR in bipolar cells by reducing NO release. In somata, inner segments and spherules of rod photoreceptors the situation was reversed, cG-IR was undetectable in the presence of NO-donors or gluta mate, was moderate in IBMX-treated retinae, but increased strongly in the presence of NOS inhibitors or GABA/glycine. We conclude that NO is released endogenously in the retina. In the presence of NO, cGMP leve ls are increased in neurons of the inner retina, but are decreased in rods.