NEW YORK (Reuters Health) Jan 04 - Experimental advances in nerve protection, regeneration, and repair should soon make possible the restoration of sight in patients affected by optic nerve damage, asserts Johns Hopkins Hospital researcher Dr. Neil R. Miller.
"Any type of damage to the optic nerve could potentially be amenable to treatment," Dr. Miller told Reuters Health. "We hope to preserve or restore vision to patients of virtually any age." This includes patients with optic nerve trauma, hereditary or metabolic problems, optic neuritis, glaucoma, and ischemic optic neuropathy. "It's not inconceivable that we could even treat optic nerve problems in utero," he added.
Apoptosis plays a major role in cell death after optic nerve injury, the Baltimore-based researcher notes in the December issue of the American Journal of Ophthalmology. Several methods have the potential to prevent or stop apoptosis, he writes. Among these are the application of inhibitors of glutamate and nitric oxide to prevent their toxic effects when released from injured retinal ganglion cells.
Alpha-2-adrenoreceptor agonists, such as brimonidine; nerve growth factors; and heat shock proteins can be applied to protect retinal ganglion cells. There is also evidence that vaccination with nonencephalitogenic peptides can protect eyes at risk for optic neuropathy.
Dr. Miller said these agents could be administered orally, by injection, or by surgically exposing the optic nerve to bathe it in a therapeutic agent. However, the most clinically feasible method, he said, would be "to inject directly into the eye and ensure selective take-up of the material by ganglion cells of the retina."
Transected nerves require an environment that will allow regeneration of the axon. One way to produce such an environment is to eliminate such inhibitory factors as myelin and myelin breakdown products. Dr. Miller also suggests provision of external growth factors, such as fibroblast growth factor and neurotrophins, to the external milieu of the axon.
In addition, molecules that guide the axons through the optic chiasm so that they synapse in the correct locations within the brain include netrins, ephrins, cadherins, and integrins.
Finally, he writes, stem cells "could replace the dead or damaged retinal ganglion cells, provide the enzymatic machinery to correct congenital or acquired metabolic defects, deliver tropic or trophic support to neural cells, provide cellular bridges among disconnected cells, or even deliver toxic substances to abnormally proliferating cells within the optic nerve."
"This is truly one of the most frustrating parts of ophthalmology," Dr. Miller told Reuters Health. "We can diagnose optic nerve conditions very well, but of all the various types of eye problems, this is the one area where treatment is incredibly lacking."
He concluded, "Only with the teamwork of physicians, drug companies, and the federal government can we solve this problem. But solve it we will." Dr. Miller hopes to see significant progress toward clinical trials within the next decade.
Am J Ophthalmol 201;132:811-818.
Copyright © 2001 Reuters Ltd
Copyright © 2001 Reuters Ltd