Localization and roles of cyclic nucleotide systems in retina.

The distribution of cyclic GMP, cyclic AMP and related enzymes in the vertebrate retina, together with factors regulating their levels, are described. Photo-receptor cells in retinas from all species examined contain very high levels of cyclic GMP and high activities of both guanylate cyclase and cyclic GMP phosphodiesterase. In more proximal regions of the retina, cyclic GMP is found at concentrations similar to that of brain. Guanylate kinase and GDP kinase, enzymes involved in GMP metabolism, also have increased activities in photoreceptor cell layers although their pattern of distribution does not exactly parallel that of cyclic GMP. The concentration of cyclic AMP is fairly uniform throughout the retina and at a level similar to that found in other areas of the CNS. However adenylate cyclase has an uneven distribution with particularly high activity in the inner plexiform layer. Cyclic nucleotide levels in retina may be modified by several factors. Light decreases both cyclic nucleotides in rod-dominant retinas, although we have not observed similar changes in cone-dominant retinas. Anoxia or ischemia elevates cyclic AMP and decreases cyclic GMP, similar to other areas of CNS, while incubation of retina in Ca(++)- free media markedly increases cyclic GMP levels, an effect opposite that seen in brain tissue. Depolarization of retina with high K(+) causes a modest elevation of cyclic AMP but has no effect on cyclic GMP, which is also significantly different from the response in brain. Cyclic AMP levels in retina however, can be elevated by dopamine which is an effect similar to that in striatum. These data indicate that there are probably multiple cyclic GMP and cyclic AMP systems in retina, some of which may be unique to this tissue.