Melatonin: An underappreciated player in retinal physiology and pathophysiology

Abstract

In the vertebrate retina, melatonin is synthesized by the photoreceptors with high levels of melatonin at night and lower levels during the day. Melatonin exerts its influence by interacting with a family of G-protein-coupled receptors that are negatively coupled with adenylyl cyclase. Melatonin receptors belonging to the subtypes MT1 and MT2 have been identified in the mammalian retina. MT1 and MT2 receptors are found in all layers of the neural retina and in the retinal pigmented epithelium. Melatonin in the eye is believed to be involved in the modulation of many important retinal functions; it can modulate the electroretinogram (ERG), and administration of exogenous melatonin increases light-induced photoreceptor degeneration. Melatonin may also have protective effects on retinal pigment epithelial cells, photoreceptors and ganglion cells. A series of studies have implicated melatonin in the pathogenesis of age-related macular degeneration, and melatonin administration may represent a useful approach to prevent and treat glaucoma. Melatonin is used by millions of people around the world to retard aging, improve sleep performance, mitigate jet lag symptoms, and treat depression. Administration of exogenous melatonin at night may also be beneficial for ocular health, but additional investigation is needed to establish its potential.

Role of Melatonin and Dopamine in the Regulation of Retinal Circadian Rhythms

“…In humans, melatonin receptors (MT 1 and MT 2 ) have been located on the rod photoreceptors and on RGCs [ 54 -56 , 62 ]. The colocalization of MT 1 and MT 2 receptors in photoreceptors suggests that these receptors may form heteromeric complexes in vivo, as demonstrated previously in vitro [ 63 , 64 ].…”

Melatonin and amfenac modulate calcium entry, apoptosis, and oxidative stress in ARPE-19 cell culture exposed to blue light irradiation (405 nm)

“…3 Melatonin is well-known to have a higher antioxidant capacity than that any of other antioxidants such as vitamin E, it may also have protective effects on different types of retinal cells including RPE cells and photoreceptors. 30 Osborne et al 31 showed that melatonin can protect cultured retinal pigment cells from oxidative damage and cell death induced by ischemia and reperfusion model. Moreover, Liang et al 32 demonstrated that melatonin has a critical role on prevention against degeneration in photoreceptors of rds mutant mice.…”

Therapeutic benefit of melatonin in refractory central serous chorioretinopathy

“…6,7 Besides the pineal gland, melatonin is also biosynthesized in the retina, where it behaves as an endogenous neuromodulator. 8 Although it has been shown that melatonin may provide neuroprotection in different systems, 9 the full range of actions of melatonin is still not completely known. In that context, experimental evidence supports the actions of it and its metabolites as a direct and indirect antioxidant, 10,11 scavenging free radicals, 11 stimulating antioxidant enzymes, 12 and enhancing the activities of other antioxidants.…”