C. Nucci et al. (Eds.)

Progress in Brain Research, Vol. 173

ISSN 0079-6123

Copyright r 2008 Elsevier B.V. All rights reserved

CHAPTER 39

Rational basis for the development of coenzyme Q10 as a neurotherapeutic agent for retinal protection

1Department of Pharmacobiology, University of Calabria, 87036 Arcavacata di Rende, Italy 2Department of Pharmacobiological Sciences, University ‘‘Magna Graecia’’ of Catanzaro, 88100 Catanzaro, Italy

3Department of Biopathology, University of Rome ‘‘Tor Vergata’’, 00133 Rome, Italy

4Mondino-Tor Vergata’’ Center for Experimental Neurobiology, University of Rome ‘‘Tor Vergata’’, 00133 Rome, Italy 5IRCCS Fondazione Istituto Neurologico ‘‘C. Mondino’’, 27100 Pavia, Italy

6University Center for Adaptive Disorders and Headache (UCHAD), Section of Neuropharmacology of Normal and Pathological Neuronal Plasticity, University of Calabria, 87036 Arcavacata di Rende, Italy

Abstract: Glaucoma is a worldwide leading cause of irreversible vision loss characterized by progressive death of retinal ganglion cells (RGCs). In the course of glaucoma, RGC death may be the consequence of energy impairment that triggers secondary excitotoxicity and free radical generation. There is substantial evidence also that a number of free radical scavengers and/or agents that improve mitochondrial function may be useful as therapies to ameliorate cell death in various neurological disorders including glaucoma. Coenzyme Q10 (CoQ10), an essential cofactor of the electron transport chain, has been reported to afford neuroprotection in neurodegenerative diseases, such as Alzheimer’s and Parkinson’s diseases, and its protective effect has been attributed in part to its free radical scavenger ability and to a specific regulation of the mitochondrial permeability transition pore. Using an established animal model of transient retinal ischemia, we have conclusively identified a role for abnormal elevation of extracellular glutamate in the mechanisms underlying RGC death that occurs, at least in part, via activation of the apoptotic program. Under these experimental conditions, N-methyl-D-aspartate (NMDA) and non-NMDA subtype of glutamate receptor antagonists, nitric oxide synthase inhibitors, and CoQ10 afford retinal protection supporting an important role for excitotoxicity in the mechanisms underlying RGC death.

Keywords: glaucoma; excitotoxicity; oxidative stress; coenzyme Q10; microdialysis neuroprotection