CIRCADIAN RHYTHMICITY IN VERTEBRATE RETINAS - REGULATION BY A PHOTORECEPTOR OSCILLATOR

Circadian regulation of retinal function has now been shown in all classes of vertebrates and attempts are now under way to understand the mechanisms underlying this regulation. The functions and organization of retinal rhythm mechanisms seem to vary among species and types of rhythms. To some extent this reflects the experimental advantages of different systems, but it also seems to reflect real variation in control mechanisms among species. Many aspects of retinal function, from gene transcription to complex intercellular interactions, are regulated by circadian oscillators (Fig. 8). Circadian clock regulation of the visual system ranges from dramatic, spontaneous rhythmicity in melatonin synthesis and disc shedding in some species to subtle rhythmic regulation of responsiveness to light and dark signals in other species. Most of the known retinal rhythms, as well as a circadian oscillator, are localized in photoreceptors. This suggests that circadian rhythmicity is fundamental for normal photoreceptor function. Some of the intracellular and paracrine components of the pathways linking different retinal rhythms have been identified. However, because of the complex feedback interactions present in the system, it is still difficult to draw strong conclusions about the causal relationships among rhythms. For example, melatonin is rhythmic and regulates dopamine release, but it is not clear that the rhythms in dopamine are driven directly by melatonin rhythms. Dopamine can modulate melatonin rhythms, but it is not necessary for generation of those rhythms (Cahill and Besharse, 1993). The recently discovered circadian regulation of photoreceptor gene expression (Pierce et al., 1993; Yoshida et al., 1993; Green and Besharse, 1994) may underlie rhythmicity at higher levels of organization. It will be important to determine which other photoreceptor genes are also regulated by circadian mechanisms and whether common factors are involved. Mechanisms of the photoreceptor oscillator itself are now approachable in a few experimental preparations, including Xenopus eyecups and photoreceptor layers and chick retinal cell cultures (Cahill and Besharse, 1991, 1993; Pierce et al., 1993). These in vitro preparations eliminate systemic influences from the interpretation of experimental results. Furthermore, by measuring the timing of rhythmicity, it is possible to distinguish oscillator responses to experimental manipulations from acute changes in rhythmic variables. This is the key to unraveling the mechanisms underlying retinal circadian rhythmicity. © 1995.