Paracrine neuroprotective effect of nitric oxide in the developing retina.
The retina of newborn rats consists of the ganglion cell layer (GCL), the inner plexiform layer (IPL), the inner nuclear layer (INL) containing amacrine cells and the neuroblastic layer (NBL). In retinal explants, the GCL enters cell death after sectioning of the optic nerve, whereas there is almost no cell death in the NBL. When protein synthesis is inhibited with anisomycin, 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-acetylpenicillamine (SNAP) blocked cell death induced by anisomycin in the NBL, but had no effect in the GCL. Sepiapterin, a precursor of the nitric oxide synthase (NOS)-cofactor tetrahydrobiopterin also had a protective effect against anisomycin. The use of 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, an inhibitor of soluble form of guanylyl cyclase, showed that anti-apoptotic effect of SNAP is partially mediated by cGMP generated by activation of guanylyl cyclase. NADPH-diaphorase histochemistry stained cells only in the GCL and 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 induced by anisomycin in the NBL, indicates that NO produced by amacrine and ganglion cells is a paracrine modulator of cell death within the retinal tissue.
Guimarães
C
C
Instituto de Biofísica da UFRJ, Rio de Janeiro, Brazil Departamento de Farmacologia, UFSC, Florianopolis, Brazil. cinthya@biof.ufrj.br
Assreuy
J
J
Linden
R
R
D000818:Animals; D000831:Animals, Newborn; D000841:Anisomycin / Q000633:toxicity; D001120:Arginine / Q000378:metabolism / Q000494:pharmacology; D001708:Biopterins / Q000031:analogs & derivatives* / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism; D006162:Guanylate Cyclase / Q000378:metabolism; D066298:In Vitro Techniques; D009252:NADPH Dehydrogenase / Q000378:metabolism; D018696:Neuroprotective Agents / Q000378:metabolism* / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism* / Q000494:pharmacology; D019899:Paracrine Communication / Q000502:physiology*; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D011621:Pteridines / Q000494:pharmacology; D011622:Pterins; D051381:Rats; D011919:Rats, Inbred Strains; D012160:Retina / Q000166:cytology / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D026423:S-Nitroso-N-Acetylpenicillamine
D018696:Neuroprotective Agents; D011621:Pteridines; D011622:Pterins; D001708:Biopterins; D009569:Nitric Oxide; D000841:Anisomycin; D026423:S-Nitroso-N-Acetylpenicillamine; D001120:Arginine; C016727:sepiapterin; D009252:NADPH Dehydrogenase; D006162:Guanylate Cyclase; C003402:sapropterin; D010396:Penicillamine; D006152:Cyclic GMP