Glaucoma – Melatonin 1

© 2011

The role of melatonin in glaucoma: implications concerning pathophysiological relevance and therapeutic potential

            (Agorastos and Huber 2011) Download

Glaucoma is a frequent ophthalmologic condition leading to chronic progressive optic neuropathy, which can result in visual impairment and blindness. In addition, glaucoma is associated with a dysregulation of circadian rhythms, as well as with a high incidence of sleep disorders, depression, and anxiety. However, because of their high comorbidity in older age, these conditions have not received much scientific attention and are often undertreated. In the current paper, we review the available literature on the role of melatonergic mechanisms in glaucoma, regulation of circadian rhythms, and depression. The literature is presented as a narrative review, providing an overview on the most important and clinically relevant publications. Recently, there has been evidence for a progressive loss of intrinsically photosensitive retinal ganglion cells (ipRGC) because of oxidative stress in glaucoma. As ipRGC are responsible for the photic transduction to the circadian system and subsequent melatonin secretion, and melatonin is involved in the pathophysiology of circadian desynchronization, sleep disorder, and depression, an impairment of photo-dependent melatonergic signaling may be a common pathway connecting glaucoma with these comorbidities. This fact, as well as the proven retinal neuroprotective role of melatonin, suggests that melatonergic drugs provide a potentially promising treatment strategy supplementing the management of intraocular pressure by pharmacological and surgical measures. Additionally, multidisciplinary treatment focusing on depression and normalization of circadian rhythms might be beneficial for glaucoma patients. Furthermore, glaucoma might be a useful model for studying the pathophysiological interactions between the melatonergic, circadian, and mood systems.

Melatonin: a novel neuroprotectant for the treatment of glaucoma

            (Belforte, Moreno et al. 2010) Download

Glaucoma is a leading cause of blindness. Although ocular hypertension is the most important risk factor, several concomitant factors such as elevation of glutamate and decrease in gamma-aminobutyric acid (GABA) levels, disorganized NO metabolism, and oxidative damage could significantly contribute to the neurodegeneration. The aim of this report was to analyze the effect of melatonin on retinal glutamate clearance, GABA concentrations, NO synthesis, and retinal redox status, as well as on functional and histological alterations provoked by chronic ocular hypertension induced by intracameral injections of hyaluronic acid (HA) in the rat eye. In normal retinas, melatonin increased glutamate uptake, glutamine synthase activity, GABA turnover rate, glutamic acid decarboxylase activity, superoxide dismutase activity, and reduced glutathione (GSH) levels, whereas it decreased NOS activity, L-arginine uptake, and lipid peroxidation. To assess the effect of melatonin on glaucomatous neuropathy, weekly injections of HA were performed in the eye anterior chamber. A pellet of melatonin was implanted subcutaneously 24 hr before the first injection or after six weekly injections of HA. Melatonin, which did not affect intraocular pressure (IOP), prevented and reversed the effect of ocular hypertension on retinal function (assessed by electroretinography) and diminished the vulnerability of retinal ganglion cells to the deleterious effects of ocular hypertension. These results indicate that melatonin could be a promissory resource in the management of glaucoma.

Melatonin in the eye: implications for glaucoma

            (Lundmark, Pandi-Perumal et al. 2007) Download

Melatonin synthesis occurs in the retina of most animals as well as in humans. Circadian oscillators that control retinal melatonin synthesis have been identified in the eyes of different animal species. The presence of melatonin receptors is demonstrable by immunocytochemical studies of ocular tissues. These receptors may have different functional roles in different parts of the eye. In view that melatonin is a potent antioxidant molecule, it can be effective in scavenging free radicals that are generated in ocular tissues. By this mechanism melatonin could protect the ocular tissues against disorders like glaucoma, age-related macular degeneration, retinopathy of prematurity, photo-keratitis and cataracts. Although an increased intraocular pressure is an important risk factor in glaucoma, other concomitant phenomena like increased glutamate levels, altered nitric oxide metabolism and increased free radical generation seem to play a significant role in its pathogenesis. Data are discussed indicating that melatonin, being an efficient antioxidant with antinitridergic properties, has a promising role in the treatment and management of glaucoma.

Melatonin as a therapeutic tool in ophthalmology: implications for glaucoma and uveitis

            (Rosenstein, Pandi-Perumal et al. 2010) Download

Several lines of evidence support the view that increased free radical generation and altered nitric oxide (NO) metabolism play a role in the pathogenesis of highly prevalent ocular diseases, such as glaucoma and uveitis. Data are discussed indicating that melatonin, being an efficient antioxidant that displays antinitridergic properties, has a promising role in the treatment of these ocular dysfunctions. Melatonin synthesis occurs in the eye of most species, and melatonin receptors are localized in different ocular structures. In view of the fact that melatonin lacks significant adverse collateral effects even at high doses, the application of melatonin could potentially protect ocular tissues by effectively scavenging free radicals and excessive amounts of NO generated in the glaucomatous or uveitic eye.


References

Agorastos, A. and C. G. Huber (2011). "The role of melatonin in glaucoma: implications concerning pathophysiological relevance and therapeutic potential." J Pineal Res 50(1): 1-7.

Belforte, N. A., M. C. Moreno, et al. (2010). "Melatonin: a novel neuroprotectant for the treatment of glaucoma." J Pineal Res 48(4): 353-64.

Lundmark, P. O., S. R. Pandi-Perumal, et al. (2007). "Melatonin in the eye: implications for glaucoma." Exp Eye Res 84(6): 1021-30.

Rosenstein, R. E., S. R. Pandi-Perumal, et al. (2010). "Melatonin as a therapeutic tool in ophthalmology: implications for glaucoma and uveitis." J Pineal Res 49(1): 1-13.