ABSTRACT
Abbreviations .................................................................................................................................203 17.1 Glaucoma .............................................................................................................................204 17.2 Melatonin in the Retina .......................................................................................................205 17.3 Oxidative Damage in Glaucoma and Melatonin as a Retinal Antioxidant .........................205 17.4 Nitrosative Stress in Glaucoma and Antinitridergic Effects of Melatonin .........................207 17.5 Excitotoxicity in Glaucoma and the Effect of Melatonin on Glutamate
Retinal Synaptic Levels .......................................................................................................208 17.6 GABAergic Dysfunction in Glaucoma and the Effect of Melatonin
on the Retinal GABAergic System ...................................................................................... 210 17.7 Effect of Melatonin on Glaucomatous Damage .................................................................. 211 17.8 Glaucoma, Circadian Rhythms, and Melatonin .................................................................. 213 17.9 Conclusions .......................................................................................................................... 215 References ...................................................................................................................................... 215
mRGCs Retinal ganglion cells expressing melanopsin RGC Retinal ganglion cell ROS Reactive oxygen species SCN Suprachiasmatic nuclei SOD Superoxide dismutase
More than 60 million people around the world are affected by glaucoma, and it has been estimated that ∼8 million suffer from bilateral blindness caused by this disease (Quigley and Broman 2006). Glaucoma is characterized by specic visual eld defects due to the loss retinal ganglion cells (RGCs) and damage to the optic nerve head (ONH). Visual loss often starts in the periphery and advances to involve the central vision, with devastating consequences to the patient’s quality of life (Almasieh et al. 2012). It is estimated that half of those affected may be not aware of their condition because symptoms may not occur during the early stages of the disease. When vision loss appears, considerable and permanent damage has already occurred. Medications and surgery can help to slow the progression of some forms of the disease, but at present, there is no cure. An increase in intraocular pressure (IOP) denitely plays a causal role in glaucomatous neuropathy. However, although ocular hypertension is common among open-angle glaucoma patients, only a limited subset of individuals with ocular hypertension will develop this disease (Friedman et al. 2004). Moreover, a signicant number of patients with glaucoma continue to lose vision despite responding well to therapies that lower eye pressure (Caprioli 1997; Georgopoulos et al. 1997; Harbin et al. 1976; Leske 2003). Thus, the mechanisms that lead to RGC death in glaucoma are still under debate. Since glaucoma is probably a complex and multifactorial disease, it is likely that several molecular pathways converge to induce RGC loss. Signals that promote RGC death in glaucoma might be exacerbated by risks factors, tilting the neuron’s fate toward dysfunction and demise. In recent years, there has been considerable progress in our understanding of multiple pathways that lead to RGC degeneration following optic nerve injury. This body of work has notably increased our knowledge of RGC neurobiology (Almasieh et al. 2012). In this vein, several factors such as a glutamate excitotoxicity (Moreno et al. 2005a), decrease in gamma aminobutyric acid (GABA) levels (Moreno et al. 2008), reduced antioxidant defense system activity (Aslan et al. 2008; Tezel 2006), and an increase in the nitridergic pathway activity (Belforte et al. 2007; Neufeld et al. 1999) have been suggested as possible additional causes for early or advanced stages of glaucomatous damage. Although the current management of glaucoma is mainly directed at the control of IOP, a therapy that prevents the death of ganglion cells should be the main goal of treatment.
