Neuroprotection in relation to retinal ischemia and relevance to glaucoma

被引:338
作者
Osborne, NN [1 ]
Ugarte, M [1 ]
Chao, M [1 ]
Childlow, G [1 ]
Bae, JH [1 ]
Wood, JPM [1 ]
Nash, MS [1 ]
机构
[1] Univ Oxford, Nuffield Lab Ophthalmol, Oxford OX2 6AW, England
关键词
apoptosis; excitotoxicity; ganglion cell death; glaucoma; glutamate; intraocular pressure; ischemia; neuroprotection; retina;
D O I
10.1016/S0039-6257(99)00044-2
中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
Management of glaucoma is directed at the control of intraocular pressure (IOP), yet it is recognized now that increased IOP is just an important risk factor ill glaucoma. Therapy that prevents the death of ganglion cells is the main goal of treatment, but an understanding of the causes of ganglion cell death and precisely how it occurs remains speculative. Present information supports the working hypothesis that ganglion cell death may result fi om a particular form of ischemia. Support for this view comes from the fact that not all types of retinal ischemia lead to the pathologic findings seen in glaucomatous retinas or to cupping in the optic disk area. Moreover, in animal experiments in which ischemia is caused by elevated IOP, a retinal abnormality similar to that seen in true glaucoma is produced, whereas after occlusion of the carotid arteries a different pattern of damage is found. In ischemia, glutamate is released, and this initiates the death of neurons that contain ionotropic glutamate (NMDA) receptors. Elevated glutamate levels exist in the vitreous humor of patients with glaucoma, and NMDA receptors exist on ganglion cells and a subset of amacrine cells. Experimental studies have shown that a variety of agents can be used to prevent the death of retinal neurons (particularly ganglion cells) induced by ischemia. These agents are generally those that block NMDA receptors to prevent the action of the released glutamate or substances that interfere with the subsequent cycle of events, that lead to cell death. The major causes of cell death after activation of NMDA receptors are the influx of calcium into cells and the generation of free radicals. Substances that prevent this cascade of events are, therefore, often found to act as neuroprotective agents. For a substance to have a role as a neuroprotective agent in glaucoma, it would ideally be delivered topically to the eye and used repeatedly. It is, therefor fore, of interest that betaxolol, a beta-blocker presently used to reduce IOP in humans, also has calcium channel-blocking functions. Moreover. experimental studies show that betaxolol is an efficient neuroprotective agent against retinal ischemia in animals, when injected directly into the eye or intraperitoneally. (C) 1999 by Elsevier Science Inc. All rights reserved.
引用
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页码:S102 / S128
页数:27
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