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See also comment(s) by Robert Ritch •
Glaucomatous optic neuropathy implies loss of retinal ganglion cells, including their axons, and a major tissue remodeling, especially in the optic nerve head. Although increased intraocular pressure is a major risk factor for glaucomatous optic neuropathy, there is little doubt that other factors such as ocular blood flow play a role as well. Mechanisms leading to glaucomatous optic neuropathy are not yet clearly understood. There is, however, increasing evidence that both an activation of glial cells and an oxidative stress in the axons play an important role. Glial cells may be activated by mechanical stress via activation of the epidermal growth-factor-receptor, or by ischemic stress via an increase in endothelin. Several factors can systemically or locally increase oxidative stress. In glaucoma, an unstable ocular blood flow leading to repeated mild reperfusion seems to be most relevant in inducing oxidative stress. The simultaneous production of nitric oxide in the astrocytes and of superoxide in the mitochondria of the axons leads to the production of the damaging peroxynitrite. Therapeutically, we need to reduce intraocular pressure, stabilize ocular blood flow, and reduce oxidative stress. Various natural compounds possess potential antioxidative value. Reduction of oxidative stress at the level of mitochondria can be achieved by gingko biloba. Polyphenolic compounds, such as tea, red wine, dark chocolate, or coffee have antioxidative properties. Coffee contains 3-methyl-1,2-cyclopentanedione (MCP), capable of scavenging peroxynitirite. Red wine-polyphenols (e.g., resveratrol), exert vasoprotective effects by inhibiting the synthesis of endothelin-1. Dark chocolate decreases blood pressure and improves endothelium-dependant vasorelaxation. Anthocyanosides (bilberries) owe their antioxidant effects to their particular chemical structure. Other antioxidants include ubiquinone and melatonin.
Dr. M. Mozaffarieh, Department of Ophthalmology, University Hospital Basel, Basel, Switzerland