Fabian S Lerner

Brain antioxidant status in a high pressure-induced rat model of glaucoma.

Purpose:  The goal of the present study is to establish the antioxidant status in the brain of a high pressure–induced rat model.

Evidence of Oxidative Stress Damage in Glaucoma

Oxidative stress has been implicated as a risk factor at several levels in the pathophysiology of glaucoma (Ferreira et al., 2004, 2009, 2010) as well as neurodegenerative diseases (Famulari et al., 1996); growing evidence supports the role of oxidative stress in glaucomatous neurodegeneration (Tezel, 2006). Reactive oxygen species are involved in signalling pathways during retinal ganglion cells death by acting as second messengers and/or modulating protein functions (Neufeld et al., 1999). Evidence of oxidative and nitrative processes was found in glaucoma in terms of activity of antioxidant enzymes, levels of low-molecular weight antioxidants and markers of lipid peroxidation (Aslan et al., 2008). Moreover it has been reported that nitric oxide may be an important mediator in retinal ganglion cells death in glaucoma (Neufeld et al., 1997). In the glaucoma eye, an altered oxidant/antioxidant balance may result in a number of molecular changes that contribute to the development of this ocular disease. Glaucoma is a disease characterized by a specific pattern of optic nerve head and visual field damage in which if it is not controlled may lead to blindness. Although it has been traditionally associated with high intraocular pressure (IOP), glaucoma is now considered as a multifactorial disease. In this context, IOP is the most important known risk factor for the development of glaucomatous optic nerve damage. Even in normal-pressure glaucoma, reducing IOP can be beneficial in terms of halting visual field damage progression. However, lowering IOP may not be enough in every case, since different mechanisms that may or may not depend on the IOP level could contribute to this damage. Proposed mechanisms include ischemia (Lander, 1982), obstruction of axoplasmic flow (Anderson & Hendrickson 1974) and deprivation of one or more trophic factors (Quigley et al., 1995), excitoxicity (Vorwerk et al., 1997) and oxidative stress damage (Ferreira et al., 2004, 2009, 2010). IOP is not elevated in all the eyes that exhibit characteristics of glaucomatous neurodegeneration but experimental elevation of IOP induces oxidative stress in the retina. Aqueous humor is known to contain several active oxidative agents such as hydrogen peroxide and superoxide anion. Low molecular weight antioxidants, such as glutathione (GSH), and ascorbate, together with molecules with free radicals scavenging properties like cysteine and tyrosine, have been identified in the aqueous. Ascorbate is present at high concentrations in it (1-2 mM) (Richer & Rose, 1998) and antioxidant enzymes such as