Oxidative Stress in Optic Neuropathies

Abstract

Increasing evidence indicates that changes in the redox system may contribute to the pathogenesis of multiple optic neuropathies. Optic neuropathies are characterized by the neurodegeneration of the inner-most retinal neurons, the retinal ganglion cells (RGCs), and their axons, which form the optic nerve. Often, optic neuropathies are asymptomatic until advanced stages, when visual impairment or blindness is unavoidable despite existing treatments. In this review, we describe systemic and, whenever possible, ocular redox dysregulations observed in patients with glaucoma, ischemic optic neuropathy, optic neuritis, hereditary optic neuropathies (i.e., Leber's hereditary optic neuropathy and autosomal dominant optic atrophy), nutritional and toxic optic neuropathies, and optic disc drusen. We discuss aspects related to anti/oxidative stress biomarkers that need further investigation and features related to study design that should be optimized to generate more valuable and comparable results. Understanding the role of oxidative stress in optic neuropathies can serve to develop therapeutic strategies directed at the redox system to arrest the neurodegenerative processes in the retina and RGCs and ultimately prevent vision loss.

Keywords: glaucoma; mitochondria; optic disc drusen; optic neuropathy; oxidative stress; redox dysregulations; retinal ganglion cell.

Figure 1

Cellular organization of the retina and location of retinal ganglion cells. Retinal ganglion cells (RGCs) localize in the innermost retinal cell layer, only separated from the vitreous humor (VH) by the inner limiting membrane (ILM). In the retina, RGCs receive inputs from amacrine cells (A) and bipolar cells (Bi), which at the same time gather visual information from the retinal photoreceptors (PR), the rods and cones. The axons of RGCs join in the nerve fiber layer (NFL) and exit the retina at the optic nerve head (ONH) to integrate the optic nerve (ON), which projects to several brain nuclei. Abbreviations: inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), outer limiting membrane (OLM), photoreceptor layer (PhL), retinal pigment epithelium (RPE), basal membrane (BM), choriocapillaris (Ch).

Figure 2

Generation of reactive oxygen and nitrogen species (RONS) by the electron transport chain. RONS are mainly generated during the last phase of cellular respiration, i.e., the electron transport chain, due to electron leakage from complex I (CI) and CIII. Mitochondria exhibit mechanisms to eliminate RONS. However, cells require the additional contribution of antioxidant enzymes like superoxide dismutase, catalase, and glutathione peroxidase to reduce cytoplasmic RONS levels and prevent cellular damage.