Neuroprotection of retinal ganglion cells: experimental data and significance to glaucoma
Neville N Osborne, Glyn Chidlow, John PM Wood
Nuffield Laboratory of Ophthalmology, University of Oxford, Walton Street,
Oxford OX2 6AW, UK
Received 15 May 2005; accepted 13 June 2005
Correspondence and requests for reprints should be addressed to:
Prof. Neville Osborne
Nuffield Laboratory of Ophthalmology
University of Oxford
Walton Street
Oxford OX2 6AW
United Kingdom
Tel: + 44 1865 248996
Fax: + 44 1865 794508
E-mail: neville.osborne@eye.ox.ac.uk
Abstract
A popular hypothesis that has been proposed to account for retinal ganglion cell death in glaucoma is that it is triggered by insults to both nerve axons and glial cells in the optic nerve head. Support for this notion comes from pathological studies on eyes of glaucoma subjects, clinical observations of patients, and laboratory studies using a variety of animal models. For example, the majority (approximately five-sixths) of all glaucoma patients have intraocular pressure that is elevated to some degree and this is known to cause a reduced perfusion pressure in blood vessels associated with the optic nerve head. In animal experiments, where ischemia is induced by artificially elevating intraocular pressure, resultant retinal pathology is not dissimilar from that seen in true glaucoma.
Experimental studies have shown that retinal ganglion cells can be induced to die by many different types of insults. Moreover, a variety of agents can be used to prevent cell death in such models. In the case of retinal ischemic paradigms, these agents are generally those that block glutamate receptors. These thereby prevent the action of released glutamate or substances that interfere with any subsequent events leading to cell death. The major factors causing cell death following glutamate receptor activation are thought to be calcium influx into cells and free radical generation. Substances that prevent such events are therefore generally found to exhibit neuroprotection. It is further thought that during the pathogenesis of glaucoma, tissue levels of glutamate and other potential toxins such as nitric oxide are elevated, and that these factors play a part in initiating the death of neurones such as ganglion cells.
Finally, the use of a single substance to attenuate retinal ganglion cell death is unlikely to form a successful neuroprotective treatment strategy for glaucoma. This is simply because such a substance would need to be both potent in its neuroprotective action and have no major side effects. It is proposed that attenuating various steps in the pathogenesis of glaucoma would form a better strategy. This would require a cocktail of less potent drugs, with differing targets.
Key Words
Retina, ganglion cell, glaucoma, glutamate, ischemia, neuroprotection
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