Functional localization of the nitric oxide/cGMP pathway in the salamander retina.

AbstractNitric oxide (NO) is a gaseous neuromodulator that has physiological functions in everycell type in the retina. Evidenceindicates that NO often plays a role in the processing of visual information in the retina through the second messengercyclic guanosine monophosphate (cGMP). Despite numerous structural and functional studies of this signaling pathwayin the retina, none have examined many of the elements of this pathway within a single study in a single species. Inthisstudy,theNO/cGMPpathwaywaslocalizedtospecificregionsandcelltypeswithintheinnerandouterretina.Wehaveimmunocytochemically localized nitric oxide synthase, the enzyme that produces NO, in photoreceptor ellipsoids,four distinct classes of amacrine cells, Mu¨ller and bipolar cells, somata in the ganglion cell layer, as well as in processeswithin both plexiform layers. Additionally, we localized NO production in specific cell types using the NO-sensitivedye diaminofluorescein. cGMP immunocytochemistry was used to functionally localize soluble guanylate cyclase thatwas activated by an NO donor in select amacrine and bipolar cell classes. Analysis of cGMP and its downstream target,cGMP-dependent protein kinase II (PKGII), showed colocalization within processes in the outer retina as well as insomata in the inner retina. The results of this study showed that the NO/cGMP signaling pathway was functional and itscomponents were widely distributed throughout specific cell types in the outer and inner salamander retina.Keywords: NO, cGMP, sGC, PKG, RetinaNitric oxide (NO) and neuronal nitric oxide synthase (nNOS) havebeen localized in every cell type in the retina, and the NO/cyclicguanosine monophosphate (cGMP) signaling pathway is involvedat several levels of visual processing and in several retinalpathologies (Goldstein et al., 1996; Eldred, 2000). The NO/cGMPpathway is predominantly activated by an increase in intracellularCa