Oxidative stress and potential applications of free radical scavengers in glaucoma

Abstract

Glaucoma is the leading cause of irreversible blindness in industrialized countries and comprises a group of diseases characterized by progressive optic nerve degeneration. Glaucoma is commonly associated with elevated intraocular pressure due to impaired outflow of aqueous humor resulting from abnormalities within the drainage system of the anterior chamber angle (open-angle glaucoma) or impaired access of aqueous humor to the drainage system (angle-closure glaucoma). Oxidative injury and altered antioxidant defense mechanisms in glaucoma appear to play a role in the pathophysiology of glaucomatous neurodegeneration that is characterized by death of retinal ganglion cells. Oxidative protein modifications occurring in glaucoma serve as immunostimulatory signals and alter neurosupportive and immunoregulatory functions of glial cells. Initiation of the apoptotic cascade observed in glaucomatous retinopathy can involve oxidant mechanisms and different agents have been shown to be neuroprotective. This review focuses on the molecular mechanisms of oxidant injury and summarizes studies that have investigated novel free radical scavengers in the treatment of glaucomatous neurodegeneration.

Figure 1.

The structures of the eye and formation of aqueous humor.

Figure 2.

Intrinsic and extrinsic pathways for apoptosis. The extrinsic pathway can be induced by members of the TNF family receptors such as tumor necrosis factor receptor (TNFR) and FAS. The intrinsic pathway can be activated by release of cytochrome c from mitochondria. In the cytosol, cytochrome c binds and activates Apaf-1, allowing it to bind and activate caspase-9. Caspase-9 and -8 activate caspase-3. Apaf-1, apoptotic protease-activating factor-1; Cyt c, cytochrome c; JNK, c-Jun N-terminal kinase; p38 MAPK, p38 mitogen-activated protein kinase; FASL, FAS Ligand.

Figure 3.

Scheme of retinal oxidative damage.