Neuroprotection Update
Chat Highlights
February 23, 2005

On Wednesday, February 23, 2005, Dr. Jeffrey Henderer, a glaucoma specialist at Wills, and the glaucoma chat group discussed "Neuroprotection Update."

Moderator:  Good evening, Dr. Henderer.  Great to have you back in the chat room.

Dr. Jeff Henderer:  I have some good news to report.  Just today I received an e-mail message describing information due to come out next week.  For the first time, researchers have demonstrated that it is possible to grow optic nerve tissue and make it connect to the brain!

P:  What do you mean by "connect" the optic nerve tissue to the brain?

Dr. Jeff Henderer:  I confess the message was a bit skimpy on that detail, but what I believe the investigators found was that they could trace nerve cells from the eye to brain.  The next step is to see if that means actual vision resulted.  Tough to do in a mouse.

Moderator:  Dr. Jeff, can you elaborate?

Dr. Jeff Henderer:  The study by Dr. Dong Feng Chen at Harvard involved mice.  The mice were specially grown, with mutations in a couple important genes that seem to regulate the growth of nerve cells.  Dr. Dong Feng Chen has presented her work at Wills.  The research was very well designed.  (See: http://www.willsglaucoma.org/searchlight/vol11no1.html#6)

Moderator:  Were stem cells used?

Dr. Jeff Henderer:  No stem cells; just mutated mice.  You are right that unless you can induce mutations in humans somehow, stem cells would be another way to try to regenerate tissue.

P:  Who funded the research?

Dr. Jeff Henderer:  Interestingly, it was funded in part by the Defense Department, which has a small epidemic of soldiers who have suffered severe battle trauma and who are surviving in record numbers.  These soldiers suffer from nerve injury, so they might benefit from this research.

P:  Do the optic nerves of the right and left eyes connect at some place before they reach the brain, or do they transmit the signals, independent of each other, to the brain?

Dr. Jeff Henderer:  Both are true. Part of each optic nerve "crosses," so that by the time the signals reach the brain, the right part of vision in each eye ends up in the left brain, and the left part of vision in each eye ends up in the right brain.

Moderator:  Is neuroprotection a relatively new medical term, or has it been around in fields other than glaucoma for awhile?

Dr. Jeff Henderer:  It turns out that glaucoma is only one of a number of chronic "neurodegenerative" diseases that affect the brain.  Alzheimers is one. Spinal cord injury is another. Spinal cord injury is often from trauma, which isn't quite the same, but the idea is that somehow the central nervous system can be tricked into regenerating.

Moderator:  Are researchers in other fields sharing information about neuroprotection?

Dr. Jeff Henderer:  Yes, there is collaboration by researchers in other fields.  For instance, I was involved for a couple years with a researcher at Jefferson Medical College who was interested in Parkinson's disease.  We were trying to test a new drug for its effect on glaucoma.

P:  In recent years, neuroprotection has received a lot of attention.  Is there much interest in obtaining effective vasoprotection in glaucoma patients?

Dr. Jeff Henderer:  I'm not sure that we have an easy way to control the blood perfusion of the eye.  The eye, like a lot of organs, autoregulates its blood pressure.  It may be the loss of this autoregulation that might cause some of the trouble, or it might not be. No one is quite sure.

P:  What do the terms "neuroprotection" and "vasoprotection" mean?

Dr. Jeff Henderer:  Neuroprotection is a general term that means "protecting the nerve from damage." Vasoprotection means preventing damage induced by blood pressure, or some form of blood-induced problem.  There has been a link between low blood pressure and glaucoma.

P:  According to that definition of neuroprotection, isn't a procedure like SLT (Selective Laser Trabeculoplasty) neuroprotective?

Dr. Jeff Henderer:  Sure.  Taken broadly, any treatment that lowers IOP (intraocular pressure), which would include trabeculectomy, is neuroprotective.

P:  Is neuroprotection in glaucoma mostly concerned with the elements of the eyes themselves, or do other body factors play a role?  I have normal-tension glaucoma, and don't know why.

Dr. Jeff Henderer:  I'm not sure we have a good understanding of exactly why some people seem to be able to tolerate high pressures without suffering damage and some can't tolerate even normal pressures.  But neuroprotection really means protection for any nerve cell in the body.

P:  I guess what I am wondering is if studies of neuroprotection take into account the other body issues that may be contributory.

Dr. Jeff Henderer:  To be honest, I'm not sure that I have a good answer for you.  It is true that at one level all diseases of the nervous system might have a common pathway through which the cells die. For instance, that could mean treatment for Parkinson's disease might help glaucoma.

P:  Are there categories describing nerve functioning besides "dead" and "alive?"

Dr. Jeff Henderer:  The answer, I believe, is yes. Some cells are "damaged," but not dead.  That's an assumption, though, because I have no way of measuring cell metabolism - - yet.  Dr. Jonathan Myers at Wills is involved with a new camera that will measure the metabolism of the retina.  The hope is that the camera will be able to show us which cells are "dead" and which are "damaged."

P:  Are the nerves of the eye arranged in bundles?  Do they correspond to the squares in the visual field?  Does damage spread within a bundle, just due to proximity?

Dr. Jeff Henderer:  Yes, the cells are arranged in a pattern that is common to all people.  The typical glaucoma patient will suffer continued damage in a region that is already damaged before developing damage in a new area, but eventually all areas can be affected.

P:  What are some promising neuroprotective agents and how do they work?

Dr. Jeff Henderer:  Well, we have shown that lower intraocular pressure (IOP) is neuroprotective.  I'm not sure that memantine is going to pan out.

P:  It must be frustrating for doctors to be committed to a study such as memantine and then discover that it may not pan out.

Dr. Jeff Henderer:  Yes, I agree. I don't know that for sure, but there have been no results published so far.  We await the publications to know what the actual results are.

P:  Is lowering IOP the only neuroprotective measure known today?

Dr. Jeff Henderer:  The only proven way of protecting the optic nerve in glaucoma is lowering the IOP.

P:  Aren't some nerves capable of regaining function naturally?  If so, what capacity or substance or activity of the body "protects" those nerves, and why wouldn't this self-healing be possible for all nerves?

Dr. Jeff Henderer:  It is true that the peripheral nerves can regenerate.  Why they can and the central nervous system can't is a mystery.  I don't know why there is this difference.

P:  What are peripheral nerves?

Dr. Jeff Henderer:  Peripheral nerves are those that travel from the spinal cord to the skin or wherever.  The central nerves are those that travel from the brain to the spinal cord.

P:  Is it true that the body's natural response to injury actually causes further damage to nerve tissue?  If so, then one approach might be to somehow discourage this reaction, somewhat as allergic reactions are discouraged by some medications.

Dr. Jeff Henderer:  Yes, it's true that some people have found elevated levels of autoantibodies in glaucoma patients, suggesting that glaucoma might be an immune disease.  In fact, some researchers have been working on a vaccine for glaucoma.  But, for the moment, that is experimental.

P:  What is the connection between apoptosis, or the death of cells, and studies about neuroprotection?

Dr. Jeff Henderer:  It turns out that cells die in glaucoma, and many other chronic neurodegenerative diseases, by a process known as apoptosis.  That is "programmed cell death" and is a critical way the body can police itself for mutated cells that arise by cell division.  These cells die, so don't cause mischief like cancer.  Finding ways to block apoptosis might be useful for some of these diseases.

P:  Would you say that taking care of our health might be neuroprotective?  I'm referring to things like not smoking and exercise and so forth.  For example, I have normal intraocular pressure and unilateral field loss. I also have very high cholesterol, which I'm now doing something about. Isn't that action "neuro-protective"?

Dr. Jeff Henderer:  Yes.  You make a very important point.

P:  What studies are doctors at Wills involved with that might hold promise in the next few years?

Dr. Jeff Henderer:  From my perspective, we are working on ways to screen for glaucoma.  Doug Rhee is working on ways to understand how different drugs affect people.  Several people, most notably Marlene Moster, are working hard to see how surgery can be improved and how different medicines can be used most effectively.  Jay Katz is running an important trial of SLT (Selective Laser Trabeculoplasty) for the treatment of glaucoma.  That is a huge study for Wills, and we are proud he is in charge of it.

P:  Today I read an article online about Dr. Katz and SLT in the Review of Ophthalmology.

Dr. Jeff Henderer:  Great! Jay has worked very hard on this study and has done a great job.  I can't tell you how tough it is to run a study like that.  The Wills Glaucoma Research Center has helped him tremendously, too.  Lots of thanks to them for supporting us all.

P:  Don't you think that evidence of factors independent of pressure in glaucoma continues to mount?

Dr. Jeff Henderer:  Yes and no. It turns out that most people do seem to respond to IOP lowering (perhaps as many as 90% in some studies).  The remainder either do not have an IOP-induced glaucoma, did not have enough IOP lowering, or perhaps do not have glaucoma.  I just don't know that we have all the answers on that subset of people.  But there is good evidence that blood flow, for instance, affects some glaucoma patients.

P:  Is neuroprotection mainly about preventing nerve-damaging conditions?  Is it possible to make central nervous system nerves stronger, more resistant to damage?

Dr. Jeff Henderer:  Yes, at the moment that is the goal of neuroprotection.  I don't know if anyone has tried to make cells "stronger."

P:  What do you think is potentially the most promising treatment on the horizon for glaucoma patients?

Dr. Jeff Henderer:  In the short term, it would be improved IOP- lowering treatments and new medicines and new surgeries.  In the long term, it will be some form of neuroprotection, either using a virus to inject new copies of genes into the eye to repair damaged ones, or developing ways to prevent cell death, or tricking cells into growing.

P:  Some doctors say that melatonin and ginkgo biloba seem to protect the optic nerve.  What do you think?

Dr. Jeff Henderer:  I'm not sure about melatonin, but ginkgo seems to help improve the blood flow to the eye.  If you believe that poor blood flow is a problem in glaucoma, and there is evidence to support that, then such a drug might help.

P:  Is lowering IOP clearly effective for ischemic optic neuropathy (ION)? If so, would you say that ION is, in fact, glaucoma?

Dr. Jeff Henderer:  There seems to be a different mechanism behind ischemic optic neuropathy.  That seems to be a blood flow problem, and the damage to the nerve is pallor of the nerve, not cupping of the nerve.  I have asked Alon Harris why he believes blood flow is a problem in glaucoma, when the classic blood flow- optic nerve problem doesn't look at all like glaucoma. He had no explanation.  The fact remains, however, that blood pressure does seem to be a risk factor.

P:  How do you check to see if you have good blood flow?

Dr. Jeff Henderer:  There is no easy way.  You could participate in a "blood flow study" at places like Indiana University with Alon Harris, or even at Wills Eye, but I'm not aware of any way you or I could check this.

[Note: Dr. Henderer will return to the chat room on March 16 to discuss research.]

End of highlights for February 23, 2005.

On March 2, Dr. Schmidt discussed "Glaucoma and the Natural Lens" in the Chat room. Click here for highlights of that meeting.

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