Ocular disorders and the utility of animal models in the discovery of melatoninergic drugs with therapeutic potential

Introduction: The pineal indole-derived hormone melatonin is a modulator of circadian and seasonal rhythms with an important role in ocular health and disease. This could be due to specific melatonin receptors that have been identified in structures such as cornea, lens, ciliary body, retina, choroid and sclera. In addition, a local synthesis of melatonin occurs in several of these ocular tissues. Areas covered: The authors review existing literature on the most common animal models where ocular melatonin actions have been tested. The therapeutic potential of melatonin in diabetic keratopathy and retinopathy, keratitis, cataracts, glaucoma, uveitis, age-related macular degeneration and retinitis pigmentosa is discussed. Furthermore, the authors comment on the usefulness of different animal models for the development of melatoninergic drugs with therapeutic potential. Expert opinion: The use of animals for the study of ocular diseases and the potentiality of melatonin and its analogs, as future therapeutic drugs, should be performed on the basis of a rationale study. It is important to note that melatonin receptors seem to be widespread all over the eye. This strongly suggests that, in order to modify the physiology and biochemistry of malfunctioning ocular tissue, the melatonin receptors which are present in that tissue must be first identified. Second there is the need to confirm that those receptors targeted perform the desirable responses, and as a third measure, to use selective agonists (or antagonists) instead of melatonin. However, although some animals mimic ocular pathologies relatively well, and these can be used in melatonin studies, there is still a long way to go till some of the results obtained in animal models could be used for human therapy.