Seeing"""""""" light and adapting to ambient light are among the most important functions of retina. How the light is """"""""seen"""""""" by the photoreceptor cells is now very well understood, and it is firmly established that a chemical, called cyclic GMP, plays a prominant role in this process. Recent studies indicate that cyclic GMP has an important role also in light adaptation. It has been shown that adaptation to bright light brings about significant changes in the retinal network, by reducing the permeability of intercellular channels, called gap junctions, between specific retinal neurons. Dopamine and nitric oxide (NO) are thought to be the mediators of this process. The present investigation is an exploratory study into understanding how NO brings about changes in the permeability of retinal gap junctions. NO is released at a greater level from the light-adapted retina, and NO increases cyclic GMP synthesis in target cells. Studies on other tissues show that when cyclic GMP influences gap junction permeability, it does so through the activation of cyclic GMP- dependent protein kinase (PKG) and phosphorylation of connexins (gap junction proteins). Based on this background, we hypothesize that light adaptation, through the activation of the NO-cyclic GMP-PKG cascade, influences the phosphorylation of specific retinal connexins. To test this hypothesis, we propose the following studies: (1) identify proteins in the whole bovine retina whole phosphorylation is affected by light adaptation, NO and cyclic GMP, (2) determine which of these proteins are connexins, and (3) study the localization of these connexins to determine if they are associated with neurons whose gap junctions are affected by light adaptation, NO and cyclic GMP. Preliminary studies have already established the presence of NO- and cyclic GMP-activated phosphorylation of several proteins in bovine retina validating the hypothesis. Successful completion of the proposed studies will, for the first time, establish the biochemical mechanism of cyclic GMP action in light adaptation, and identify the proteins that mediate its effects.
| Yevseyenkov, Vladimir V; Das, Satyabrata; Lin, Dingbo et al. (2009) Loss of protein kinase Cgamma in knockout mice and increased retinal sensitivity to hyperbaric oxygen. Arch Ophthalmol 127:500-6 |
