Nerve Regeneration and Protection
Chat Highlights – December 4, 2013
Guest Speaker – Dr. Michael Pro
Lorraine Miller, Editor, Chat Topic Researcher
Moderator: Good evening! Please welcome Dr. Michael Pro, our glaucoma expert, to this evening’s chat on “Nerve Regeneration and Protection.”
P: Dr. Pro, would you please define optic nerve regeneration and optic nerve protection for those that may not be familiar with their meaning.
Dr. Pro: Let’s cover the background first. Glaucoma is a disease where a select group of cells are damaged. These cells are the retinal ganglion cells (RCGs). They are essentially the “cables” that take the light information that is focused on the retina and send this information to the brain. The RGCs are bundled up in the optic nerve and damage to a large group of the RGCs can lead to loss of vision. It is estimated that you need to lose about fifty percent of your normal number of RGCs to have visual loss on the visual field test. The RGCs are lost in groupings and this causes change to the appearance of the optic nerve in the characteristic cupping and notching.
Neuroprotection refers to any strategy to prevent damage or death of the RGCs. You might consider lowering of the intraocular pressure (IOP) to be one major neuroprotective approach. Optic nerve regeneration refers to growing new RGCs to replace the ones lost due to glaucoma.
P: Because patients present so late in the disease, especially the silent types like open angle glaucoma, I’m anxious to bring home to patients the urgency of their making lifestyle changes to help enhance nerve protection. Can you share any new guidelines with diet or supplements?
Dr. Pro: Absolutely! In prior chats, I have discussed some lifestyle changes that may help prevent or maybe delay the progression of glaucoma. There was a recent study involving glaucoma suspect patients that had the patients engage in an exercise regimen. After several weeks, their IOP was lower. The IOP returned to baseline when they resumed a more sedentary lifestyle.
I think the dietary message is also important. There is evidence in animal studies that a diet higher in omega 3 fatty acids, like in fish oil, caused lowering of the IOP. There are larger survey studies that also support the idea that a diet more plant-based with less animal fat may be beneficial, too.
P: How would a clinician define the relative efficacy of neuroprotective agents once they are instilled in the eye?
Dr. Pro: That is the million dollar question! Currently the FDA will not consider a non-IOP or visual field endpoint in a drug study. Evaluating a drug for neuroprotection is very difficult and would require a very large scale study to try to find a visual field endpoint. This was part of the problem with the Memantine study. Memantine is a drug used for Alzheimer’s disease. It is thought to prevent cell death through the NDMA (N-methyl-D-aspartate) pathway. The data from the Memantine study did not meet its primary endpoint (visual field data).
P: Why are the two processes, regeneration and protection, combined?
Dr. Pro: They aren’t really. We are talking about them together, but if anything, we are much closer to neuroprotective agents than to regeneration. For instance, there are recent studies that suggest a neuroprotective effect from Alphagan (brimonidine).
P: There’s been a lot of talk on the Internet recently suggesting replacing the prevailing theories of ganglion cell atrophy with one of severance of fibers to explain the phenomenon of cupping and crater formation. Has work been done to prove either?
Dr. Pro: I am not sure and at this point. I think there seems to be a great deal of data that supports the idea of retinal ganglion cell atrophy and death to explain notching and cupping.
P: What are some the current neuroprotective treatments available?
Dr. Pro: The Low Pressure Glaucoma Treatment Study (LoGTS) compared timolol vs. brimonidine (Alphagan). Although more patients in the brimonidine group withdrew due to allergy, overall brimonidine patients were less likely to have visual field progression. You may also look at this study and conclude that timolol is worse due to possible decreased optic nerve perfusion. The jury is still out on timolol. There are other agents such as calcium channel blockers that have been investigated as a neuroprotectant. Ginkgo biloba is thought to improve optic nerve perfusion.
P: When the optimal neuroprotectant or regenerative agent is developed, how will it be delivered into the eye? Can you also provide an estimate as to when we might see such an agent?
Dr. Pro: I think an implant is the more likely vehicle. Implants and injections have proven very successful in retinal diseases and this makes sense for glaucoma, too. It is so difficult to guess on time to market. I can say that there are neuroprotection implants in early clinical trials. My best guess is ten years.
P: Why are human retinal ganglion cells important in this research?
Dr. Pro: The retinal ganglion cells (RGCs) are the cells that send information from the eye to the brain. They are the cells that make up the optic nerve which is like the thousands of individual fibers in a fiber optic cable.
P: Why do human retinal ganglion cells die from apoptosis (programmed cell death)?
Dr. Pro: There are many of theories. Free radical formation and excitotoxicity is one. Oxidative stress is another. Programmed cell death (apoptosis) occurs naturally and may be unregulated in glaucoma patients.
P: Can optic nerve fibers be made to grow long enough to go from eye to brain to allow visual circuits to re-form?
Dr. Pro: Regeneration has been demonstrated in a rat model. This has not been shown in humans yet. It is very complex. There are various cellular signals necessary for the cells to grow where they need to go and we don’t understand these signals very well yet.
Moderator: Thank you Dr Pro! Thank you for the great questions from around the world! See you next year!