Oxidative stress in glaucomatous neurodegeneration: Mechanisms and consequences

Abstract

Reactive oxygen species (ROS) are generated as by-products of cellular metabolism, primarily in the mitochondria. Although ROS are essential participants in cell signaling and regulation, when their cellular production overwhelms the intrinsic antioxidant capacity, damage to cellular macromolecules such as DNA, proteins, and lipids ensues. Such a state of "oxidative stress" is thought to contribute to the pathogenesis of a number of neurodegenerative diseases. Growing evidence supports the involvement of oxidative stress as a common component of glaucomatous neurodegeneration in different subcellular compartments of retinal ganglion cells (RGCs). Besides the evidence of direct cytotoxic consequences leading to RGC death, it also seems highly possible that ROS are involved in signaling RGC death by acting as a second messenger and/or modulating protein function by redox modifications of downstream effectors through enzymatic oxidation of specific amino acid residues. Different studies provide cumulating evidence, which supports the association of ROS with different aspects of the neurodegenerative process. Oxidative protein modifications during glaucomatous neurodegeneration increase neuronal susceptibility to damage and also lead to glial dysfunction. Oxidative stress-induced dysfunction of glial cells may contribute to spreading neuronal damage by secondary degeneration. Oxidative stress also promotes the accumulation of advanced glycation end products in glaucomatous tissues. It is also evident that oxidative stress takes part in the activation of immune response during glaucomatous neurodegeneration, as ROS stimulate the antigen presenting ability of glial cells and also function as co-stimulatory molecules during antigen presentation. By discussing current evidence, this review provides a broad perspective on cellular mechanisms and potential consequences of oxidative stress in glaucoma.

Mitochondrial function and redox control in the aging eye: Role of MsrA and other repair systems in cataract and macular degenerations

“…Oxidative stress is implicated in wide range of age related disorders including Alzheimer's disease, Parkinson's disease amyotrophic lateral sclerosis (ALS), Huntington's disease and the aging process itself (Lin and Beal, 2006). In the anterior segment of the eye, oxidative stress has been linked to lens cataract (Truscott, 2005) and glaucoma (Tezel, 2006) while in the posterior segment of the eye oxidative stress has been associated with macular degeneration (Hollyfield et al, 2008). Key to many oxidative stress conditions are alterations in the efficiency of mitochondrial respiration resulting in superoxide (O 2 -) production.…”

Neuroglobin Is an Endogenous Neuroprotectant for Retinal Ganglion Cells against Glaucomatous Damage

“…28 -30 Several factors, including oxidative stress, 31 mitochondrial dysfunction, 32 and glutamate neurotoxicity 33,34 are proposed to work concomitantly in the pathogenesis of the disease and in regulating RGC susceptibility to glaucomatous damage. 35,36 Given possible involvement of NGB in these cellular functions, we hypothesized that NGB plays a role in glaucoma and may represent a novel target for treatment of the disease. Recently, we and others developed a convenient method of reproducibly inducing chronic IOP elevation in mice by anterior chamber injection of polystyrene microbeads.…”

Dynamic, in vivo, real-time detection of retinal oxidative status in a model of elevated intraocular pressure using a novel, reversibly responsive, profluorescent nitroxide probe

“…Pro-oxidants are recognized as having a crucial role in various biological processes including the regulation of normal physiological processes (Morrow et al, 2010;Nathan, 2003), however in excess, can lead to an imbalance in the redox environment and lead to a variety of disorders including cancer, I/R injury, and neurodegeneration (Dirani et al, 2011;Hess and Manson, 1984;Lin and Beal, 2006;Liu et al, 2007;Morrow et al, 2010;Tezel, 2006;Yapici et al, 2011). Techniques capable of quantifying and visualising the changes to the cellular redox environment of biological systems as a result of pro-oxidant or antioxidant processes are therefore crucial for understanding the mechanistic links between free radical chemistry and disease outcomes (Morrow et al, 2010).…”