The Therapeutic Trip of Melatonin Eye Drops: From the Ocular Surface to the Retina

Abstract

Melatonin is a ubiquitous molecule found in living organisms, ranging from bacteria to plants and mammals. It possesses various properties, partly due to its robust antioxidant nature and partly owed to its specific interaction with melatonin receptors present in almost all tissues. Melatonin regulates different physiological functions and contributes to the homeostasis of the entire organism. In the human eye, a small amount of melatonin is also present, produced by cells in the anterior segment and the posterior pole, including the retina. In the eye, melatonin may provide antioxidant protection along with regulating physiological functions of ocular tissues, including intraocular pressure (IOP). Therefore, it is conceivable that the exogenous topical administration of sufficiently high amounts of melatonin to the eye could be beneficial in several instances: for the treatment of eye pathologies like glaucoma, due to the IOP-lowering and neuroprotection effects of melatonin; for the prevention of other dysfunctions, such as dry eye and refractive defects (cataract and myopia) mainly due to its antioxidant properties; for diabetic retinopathy due to its metabolic influence and neuroprotective effects; for macular degeneration due to the antioxidant and neuroprotective properties; and for uveitis, mostly owing to anti-inflammatory and immunomodulatory properties. This paper reviews the scientific evidence supporting the use of melatonin in different ocular districts. Moreover, it provides data suggesting that the topical administration of melatonin as eye drops is a real possibility, utilizing nanotechnological formulations that could improve its solubility and permeation through the eye. This way, its distribution and concentration in different ocular tissues may support its pleiotropic therapeutic effects.

Keywords: cataract; diabetic retinopathy; drug delivery; dry eye; glaucoma; macular degeneration; melatonin; myopia; nanotech formulation; uveitis.

Figure 1

Properties of melatonin and its supposed effects on the eye. Created with Servier Medical Art (https://smart.servier.com) and modified with Microsoft PowerPoint.

Figure 2

Hypothetical diffusion of melatonin in nanomicelles from the ocular surface to different eye tissues. The figure illustrates a possible ‘vertical’ diffusion, going from the ocular surface through the aqueous humor, the lens, the vitreous body to the retina; and a ‘lateral’ diffusion through the anterior uvea and the local blood circulation [50]. Created with Servier Medical Art (https://smart.servier.com) and modified with Microsoft PowerPoint.