Circadian control of photoreceptor outer segment membrane turnover in micegenetically incapable of melatonin synthesis

Vertebrate retinal photoreceptors periodically shed membrane from their out er segment distal tips, this material is phagocytosed and degraded by the r etinal pigmented epithelium. Both a circadian oscillator and the daily ligh t-dark cycle affect disk shedding, and the effects of both may be mediated by melatonin. To clarify melatonin's role in this process. we asked whether endogenous melatonin is required for rhythmic disk shedding in mouse retin a. We analyzed disk shedding in two mouse strains: C3H, which produce melat onin in retina and pineal under the control of circadian oscillators, and C 57BL/6, which do not produce melatonin. In cyclic light, both strains exhib ited a robust cycle of disk phagosome content in the pigmented epithelium. Peak shedding occurred just after dawn, and trough levels occurred during t he middle of the dark phase. In constant darkness, mice exhibited circadian rhythms of locomotor activity, the characteristics of which were similar b etween strains. Both strains also exhibited rhythmic disk shedding in const ant darkness, although amplitudes of the rhythms were damped. Exogenous mel atonin delivered once per day failed to reestablish high-amplitude cyclic s hedding in mice held in constant darkness. Our results show that, while dis k shedding in cyclic light is robustly rhythmic, neither rhythmic productio n of melatonin nor the circadian oscillator responsible for rhythmic locomo tor activity is sufficient to drive high-amplitude rhythmic shedding in con stant darkness. More importantly, melatonin is required neither for cyclic changes in the rate of disk shedding in cyclic light, nor for the circadian rhythm of disk shedding in constant darkness.