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

Abstract

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.

Effect of Melatonin and 5-Methoxycarbonylamino-N-Acetyltryptamine on the Intraocular Pressure of Normal and Glaucomatous Mice

“…Generating an artificial increase in IOP with biochemical agents (e.g., chymotrypsin) and using surgical procedures (e.g., episcleral vein cauterization or laser trabeculoplasty) are efficient protocols for elevating IOP, but these approaches damage several tissues that might be targets for reducing ocular hypertension and glaucoma. Therefore, in addition to the need for elevation of IOP, a glaucoma animal model must be minimally invasive to guarantee that most of the ocular structures will be intact and suitable for drug treatment (Crooke et al, 2012a).…”

Diadenosine tetraphosphate as a potential therapeutic nucleotide to treat glaucoma

“…Currently, however, these treatments damage several tissues that might be the targets to reduce ocular hypertension and glaucoma. Therefore, besides the necessity of an elevation of IOP, a glaucoma animal model needs to be minimally invasive in order to guarantee that most of the ocular structures will be intact and suitable for drug treatment [16].…”

Beneficial effect of the antioxidant riboflavin on gene expression of extracellular matrix elements, antioxidants and oxidases in keratoconic stromal cells

“…Theoretically, antioxidant compounds other than riboflavin could instigate the cellular alterations observed in this study. For instance, melatonin has ROS‐neutralising activity in animal models of keratitis and cataract . The use of riboflavin to detoxify ROS may be particularly expedient, as riboflavin is already safely in clinical use during collagen cross‐linking of the keratoconic cornea.…”

“…For instance, melatonin has ROSneutralising activity in animal models of keratitis and cataract. 79 The use of riboflavin to detoxify ROS may be particularly expedient, as riboflavin is already safely in clinical use during collagen cross-linking of the keratoconic cornea. Another future topic of investigation could include examining whether the continued prescription of riboflavin as an adjunct therapy improves the outcomes of collagen cross-linking by alleviating oxidative damage and facilitating healing, produced by UV irradiation and epithelial debridement during the procedure.…”