The retinae of many vertebrates have the capacity to synthesize melatonin (44). However, this source of melatonin does not appear to contribute substantially to circulating melatonin, which is pineal derived. Retinal melatonin appears to act locally as a paracrine neuromodulator and regulator of rhythmic retinal physiology (21,23). Retinal melatonin is synthesized primarily in photoreceptor cells (2,10,17,18,42) and its production is regulated by a local, retinal circadian clock (4,10,41).
Melatonin modulates the release of several neurotranmitters in the retina. It inhibits the release of dopamine (6,13) and acetylcholine (29) from amacrine cells. Melatonin stimulates the release of glutamate (15), the photoreceptor neurotransmitter. The release of dopamine and acetylcholine are stimulated by light (e.g., 5,27), while glutamate is released from photoreceptors in darkness (e.g., 34). Thus, melatonin mimics, and may partiially mediate, the effects of darkness on neurotranmitter release. The effect of melatonin on dopamine release appears particularly important, as dopamine is a mediator of circadian changes in visual sensitivity (8,26).
Melatonin promotes dark-adaptive photomechanical movements in photorecep-tors and retinal pigment epithelial (RPE) cells (11,30-32,35). Melatonin activates rod photoreceptor disk shedding and phagocytosis by RPE cells (3). Disk shedding and phagocytosis occur in a circadian fashion in most vertebrates, and melatonin may be a neurohumoral link between the retinal circadian clock and the rhythmic turnover of photosensitive outer segment membranes.
Melatonin has effects on photoreceptor survival. Its administration prior to exposure to high intensity light enhances photoreceptor degeneration in albino rats (7,25,43). In contrast, intraocular injection of the melatonin antagonist, luzindole, promotes photoreceptor survival and maintenance of function in light-damaged retinas (36). The mechanisms responsible for these effects are unknown, but may reflect the inhibitory effect of melatonin on dopamine release and loss of a neuroprotective action of dopamine (22). Alternatively, it may reflect direct effects of melatonin on photoreceptor-RPE interactions or a disruption of retinal circadian physiology.
The chicken has become an important experimental model for studying retinal melatonin biosynthesis and actions, because its retina has a relatively high density of melatonin receptors (14,33) and robustly synthesizes melatonin under the influence of a circadian clock (19). Chicken retina contains all of the enzymes of the melatonin biosynthetic pathway and readily converts [14C]trytophan to [14C]melatonin (39). Mela-tonin levels in chick retina are low during the day, but show a dramatic nocturnal increase in chicks housed under a light-dark cycle or in constant darkness (19). Acute light exposure at night rapidly reduces retinal melatonin levels. This review will focus on the regulation of two enzymes of the melatonin biosynthetic pathway, TPH and AA-NAT, and on their roles in regulating circadian melatonin biosynthesis and the acute inhibitory effect of light in the chick retina.
Was this article helpful?