Circadian Responses to Light in RD Mice of Different Ages

Abstract

Abstract: : Purpose: The progression of rod degeneration in the rd mouse commences early in postnatal development and results in a complete loss of rods by the fourth–sixth week of age. However, circadian responses to light have been shown to depend on photosensitive retinal ganglion cells (RGC). Rod degeneration is followed by a process of retinal dystrophy that finally affects all retinal cells. In the present work we studied the phase shifting of rd mice circadian activity rhythms at different ages, and in two different animal models or retinal degeneration: rd1 and rd10. These two models show a different time course in their retinal degeneration. Circadian responses to light of animals of different ages are studied in comparison with the presence and density of photosensitive RGC. Methods: The phase shifting of circadian activity rhythms was evaluated in rd1 and rd10 mice of 90, 180, 270 and 360 days of age. Animals were housed individually in cages equipped with activity wheels at a photoschedule of 12/12 hr light/dark cycle (light intensity 50 µW/cm²). Full field electroretinographic responses and immunohistochemistry for cell–type specific markers (rod photoreceptors and RGC) were tested in all animals. Results were compared with those obtained in age–matched C57/bl6 mice, used as controls. Results: Up to six months of age, dystrophic animals showed maintained circadian responses to light. After such age, rd1 mice showed a decrease in their phase shifting of circadian activity rhythms compared to control animals. Rd 10 mice showed normal circadian responses to light up to one year of life. Immunohistochemistry for photosensitive RGC closely correlated with the time course of retinal cell degeneration in dystrophic animals. Conclusions: We demonstrate that circadian responses to light is altered aging rd mice (360 days of age) although remain somehow capable of photically regulating circadian activity rhythms. Circadian responses to light parallel photosensitive RGC degeneration in rd mice.

Keywords: circadian rhythms • degenerations/dystrophies • ganglion cells