Paracrine neuroprotective effect of nitric oxide in the developing retina

The retina of newborn rats consists of the ganglion cell layer (GCL), the i nner plexiform layer (IPL), the inner nuclear layer (INL) containing amacri ne cells and the neuroblastic layer (NBL). In retinal explants, the GCL ent ers cell death after sectioning of the optic nerve, whereas there is almost no cell death in the NBL. When protein synthesis is inhibited with anisomy cin, cell death is blocked in the GCL and induced in the NBL. We tested the roles of nitric oxide (NO) on cell death in the retina in vitro. Either L- arginine, the substrate for NO synthase or the NO donor S-nitroso-acetylpen icillamine (SNAP) blocked cell death induced by anisomycin in the NBL, but had no effect in the GCL, Sepiapterin, a precursor of the nitric oxide synt hase (NOS)-cofactor tetrahydrobiopterin also had a protective effect agains t anisomycin, The use of 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, an in hibitor of soluble form of guanylyl cyclase, showed that anti-apoptotic eff ect of SNAP is partially mediated by cGMP generated by activation of guanyl yl cyclase, NADPH-diaphorase histochemistry stained cells only in the GCL a nd INL. Thus, the degenerative effect of anisomycin is observed within the NBL, whereas the localization of NOS is restricted to the GCL and INL, The protective effect of both the NO substrate and cofactor upon cell death ind uced by anisomycin in the NBL, indicates that NO produced by amacrine and g anglion cells is a paracrine modulator of cell death within the retinal tis sue. Keywords: apoptosis, cell death, neuroprotection, nitric oxide synthas e, nitric oxide, retina.