LIGHT‐INDUCED REDUCTION IN CYCLIC GMP OF RETINAL PHOTORECEPTOR CELLS IN VIVO: ABNORMALITIES IN THE DEGENERATIVE DISEASES OF RCS RATS AND rd MICE1

Abstract

Abstract— The effect of light on the content of cyclic GMP in degenerative retinae of Royal College of Surgeons (RCS) rats and rd mice was compared with that in control retinae during postnatal maturation. In vivo, the cyclic GMP content of retinae of control rats or mice is light‐dependent after photoreceptor outer segments develop. Mature retinae of control animals have high levels of cyclic GMP in the dark which are reduced 40–50% upon illumination. In the rd mouse disorder, a light‐induced reduction in cyclic GMP content is observed while the rod outer segments are morphologically intact. The rd photoreceptor cells possess a phosphodiesterase which, when stabilized by freeze‐drying, has a Km similar to that of control photoreceptors, and an apparent Vmax that is below normal. It is suggested that developing rd visual cells have an abnormality in cyclic GMP metabolism which results in the accumulation of cyclic GMP within the entire cell but which does not prevent the light‐mediated reduction of cyclic GMP in their outer segment organelles. In the RCS dystrophy, a light‐induced reduction in cyclic GMP content is observed also during the period when photoreceptor outer segments are present. The cyclic GMP content of dark‐ or light‐adapted RCS retinae is below that of the respective controls. Biochemical and morphological observations show that cyclic GMP levels increase in rd visual cells and that they are reduced in photoreceptor cells of RCS retina before the onset of visual cell degeneration. Until detailed knowledge of the role of cyclic GMP in the visual cells is known, it is suggested that high or low levels of cyclic GMP in rd and RCS photoreceptors, respectively, result from differences in the etiology or histopathology of the mouse and rat diseases.