Management of glaucoma is directed at the control of intraocular pressure (IOP), yet
it is recognized now that increased IOP isjust an important risk factor in 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 from 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, therefore, 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 neuro protective agent against retinal ischemia in animals, when injected
directly into the eye or intraperitoneally.