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Optic Nerve Axon Growth
We know that once damage from glaucoma has occurred, the damage is irreversible. The best defense against loss of vision from glaucoma is first to know you have it. This is why we stress early detection.
We are also painfully aware that despite our best efforts, some people with glaucoma will still experience vision loss. For these reasons, the area of research known as neuroprotection is of great interest to many of us. In early 2001, we talked about a drug that holds promise for protecting the optic nerve from glaucoma. Now we’re pleased to report breakthrough research that may signal the ability to actually “fix” the nerve after it’s been damaged.
We emphasize the word “may” since we are only in the “baby steps” stage of this exciting research. However, Larry Benowitz, PhD, of Children’s Hospital in Boston, MA, and also on faculty at Harvard Medical School, has recently completed a study that brings us closer to this possibility than ever before. Dr. Benowitz and his colleagues have uncovered a way to stimulate the damaged (crushed) optic nerve to regenerate its axons.
This has been done before; however, Dr. Benowitz’s research has reproduced axon regeneration in greater numbers and for much greater distances. Talking to Dr. Benowitz, one gets the distinct impression that while this is just the beginning, we’re really on to something. We at GRF are proud to have funded this research in part, along with the Mellam Family Foundation. Michal Schwartz, PhD, at the Weizmann Institute of Science in Israel, also funded by GRF, is currently carrying out related work in the area of neuroprotection.
Science and Serendipity
The cause of this axon growth was actually a surprise to the research team. As is often the case with research, we sometimes unknowingly stumble onto answers. When asked how they came up with their strategy, Dr. Benowitz chuckled, “Actually, it was an accident.” It seems they were testing the effects of certain molecules.
Dr. Benowitz and his team wanted to know what molecules would stimulate trophic (growth activating) factors that would encourage ganglion cell fiber growth. There was one molecule in particular the team was very excited about. With strong suspicions that it would do the trick, they injected this molecule, as well as other molecules, and monitored the different responses. What Dr. Benowitz referred to as their “favorite molecule” produced good results, but so did many other molecules. The task then was to figure out what was producing the growth response.
After retracing their steps, the team found that it really didn’t matter what was being injected. It turned out that the lens injury caused by injecting the molecule, and not the molecule itself, was responsible for triggering the desired response. After shrugging off their mild disappointment that it wasn’t their “favorite molecule” the team moved on - happy that axon growth was being stimulated at all.
Lens Injury Causes Axon Growth
The lens injury was producing an inflammatory response. This, in turn, provoked macrophage infiltration into the vitreous humor (the gel in the back of the eye). These macrophages are generally thought to have an adverse effect. However, in this case, at least some of them seem to be putting out trophic factors that contribute to the growth of retinal ganglion cell fibers.
Since damage to the lens is not clinically practical, the team then began to look for other ways to evoke this response. One way was to introduce a cell wall preparation from yeast. By doing this, they were able to produce axon growth without damaging the lens.
Dr. Benowitz says, “We’re not the first to discover that axons from retinal ganglion cells are able to regenerate. But it was always thought the regeneration could not penetrate the scar tissue created by the injury.” He goes on, “Up to this point, it was thought that it [the scar tissue] was an impenetrable barrier.” Almost all of the surviving retinal ganglion cells in the study reverted to growth mode. While these axons did not actually establish structural continuity and function, a fair number were able to extend through the injury site and down on to the optic nerve.
Importance for the Future of Glaucoma Treatment
Vision loss caused by glaucoma is a direct result of damage to the optic nerve. As we’ve said, there has never been (and still isn’t) a way to repair the optic nerve once damage is done. The best course of action for glaucoma has always been early detection and treatment to prevent further damage. However, since glaucoma has virtually no signs or symptoms, too often glaucoma is not discovered until damage has already occurred.
Even though once detected, most cases of glaucoma are controlled with medication or surgery, it remains the second leading cause of blindness in America. An estimated 3 million Americans have glaucoma, and of those, only half know they have it. This means that 1.5 million people may experience irreversible loss of vision because their glaucoma will go untreated, making the ability to repair the nerve vitally important.
What Comes Next?
While we are yet years from practical application of these findings, this research provides great hope for the future. Hope exists not only for glaucoma patients but also for other neurological diseases. Next steps involve further refining the process. We must know exactly which molecules are causing the growth to occur as well as which ones interfere. Once researchers refine what is needed to help the axon grow, they need to determine if those axons can navigate properly and get where they need to go. Scientists have only just begun to look into this area. This research also has not yet been conducted on the human eye.
Dr. Benowitz states, “We need to find out who are the good guys and who are the bad guys and then figure out how to tip the balance to stimulate nerve cell growth.” He goes on, “The question is not, can the nerve cell regenerate its axon, because clearly it can. We just need to identify the right stimuli that will get the neuron thinking it’s back in its youth and start growing again.” We look forward to a future fountain of youth (so to speak) for optic nerve cell axons.
This article appeared in the September 2001 issue of Gleams. Subscribe