In glaucoma, should enthusiasm about neuroprotection be tempered by the experience obtained in other neurodegenerative disorders?

Some in nitro and in vivo evidence, as well as rare observations in human eyes with glaucoma, suggests that retinal ganglion cells could be lost by apoptosis during the course of glaucomatous optic neuropathy. There exist also observations indicating that in the vitreous of patients with glaucoma it is possible to measure an increased concentration of glutamate (an excitotoxic amino acid known to induce neuronal apoptosis in animal models). These observations, among others, suggest the possibility of an excitotoxicity mechanism in the pathogenesis of glaucoma and as a consequence the potential for a neuroprotective approach to treating this disorder. Amazingly, not only in glaucoma but also in other neurodegenerative disorders (Parkinson's disease, amyotrophic lateral sclerosis, stroke, etc.) it has been postulated that neurons could be lost through an excitotoxic mechanism. In these nonglaucomatous disorders, quite a large number of clinical trials have already been conducted to determine the potential benefit of different neuroprotective therapies. Unfortunately, with a few rare exceptions, the results of these clinical studies have been very disappointing (in contrast to encouraging results obtained in preclinical trials). The experience acquired in other neurodegenerative disorders should probably be kept in mind when addressing the question of neuroprotection in glaucoma. In particular, the hope raised by preclinical studies showing that drugs could have a beneficial effect on the survival of retinal ganglion cells should certainly be tempered until such an effect is confirmed by clinical trials conducted in patients with glaucoma.