Circadian rhythms in the eye: The physiological significance of melatonin receptors in ocular tissues

Many biological processes display circadian rhythms in activity, which presumably operate to coordinate cellular functions with daily environmental oscillations. The diurnal changes in environmental illumination are conveyed by the retina to the brain to entrain circadian rhythms throughout the body. Many ocular tissues themselves exhibit circadian rhythms of activity to optimize specific processes which require coordination with the light–dark cycle. The circadian signaling molecule, melatonin, is secreted into the circulation from the pineal gland, and is also produced within specific ocular cells such as retinal photoreceptors, ciliary epithelial cells, and perhaps cells of the lens. Melatonin appears to entrain many aspects of the biological clock via activation of specific G-protein-coupled integral membrane melatonin receptors. Melatonin receptors have been identified in many ocular tissues, including the neural retina, retinal pigment epithelium, ciliary body, cornea, sclera, and lens. This review will describe the circadian rhythmicity of some of the functions of these various ocular tissues, and will attempt to correlate these circadian activities with the expression of specific G-protein-coupled melatonin receptors, the role of melatonin in the regulation of circadian activity in ocular tissues, and its potential role in ocular diseases.