Analysis of normal and rcdl Irish setter retinal proteins

In both of the early onset systems, the rd mouse and the rcdl Irish Setter, early elevation of cyclic GMP may be the ultimate cause of accelerated photoreceptor degeneration. This would be consistent with the data utilizing in vitro systems in which retinal samples, in culture, undergo degeneration in response to constant exposure to high levels of this nucleotide. However, the ultimate cause of the elevated cyclic GMP in the rd mouse or in the rcdl Irish Setter still remains a mystery. It appears that all of the necessary proteins of the visual cascade are produced, although they are lost at different rates. The phosphodiesterase appears to be reduced faster than other proteins. This may, in turn, account for the elevation in cyclic GMP levels. The cause of this enhanced disappearance could reside in the phosphodiesterase protein itself, or in other more distal components. The alteration in rhodopsin reaction to the specific rhod-4 antisera suggests that this protein is not properly oriented in the disc membrane. Although this may or may not alter the visual cascade, it does suggest that these membranes are not identical to those of the normal dog retina. Future studies should focus on the individual functional activities of each component, on their structures, and on their proper assembly within the disc.