Chat Highlights
Neuroprotection
October 10, 2001

Norma Devine, Editor

On Wednesday, October 10, 2001, Dr. Jeff Henderer, a glaucoma specialist at Wills, and the glaucoma chat group discussed "Neuroprotection." 

Moderator:  Tonight the topic is neuroprotection.  Dr. Jeff Henderer is our guest.  Dr. Jeff, what does neuroprotection mean?

Dr. Jeff Henderer:   Neuroprotection means that the optic nerve is being prevented from dying.  In animal studies, some drops appear to prevent nerve damage in ways not related to lowering pressure.

P:  It is claimed that several kinds of eye drops provide neuroprotection.  Is there any evidence that they protect the optic nerve in ways other than lowering intraocular pressure?  

Dr. Jeff Henderer:  Well, remember that neuroprotection means preventing the nerve from being damaged.  All drops are "neuroprotective" in that they lower IOP, which is the proven way to prevent nerve damage.  Others that may go beyond that are Alphagan, Betoptic S, and perhaps Trusopt and Travatan.

P:  What's so special about Betoptic S?  Isn't it just a selective beta blocker?  

Dr. Jeff Henderer:  It is thought that it may also have calcium channel blocking capabilities, which may be protective.

P:  So these other neuroprotectors don't lower pressure; they only protect the nerve?

Dr. Jeff Henderer:  Yes. 

P:  I am aware of two theories on neuroprotection.  One is to prevent cell apoptosis;  the other is to improve vascular health for healthier ganglia.  Are there others and do you favor one theory over the other?

Dr. Jeff Henderer:  Well, they might actually be related in some ways.  We probably don't fully understand how, but ischemia can trigger apoptosis, as well as toxic compounds, so there might be several triggers to lead to the final common pathway of apoptotic cell death.

P:  What is "apoptosis?"

Dr. Jeff Henderer:  Apoptosis is a natural process of programmed cell death, or suicide.  It is common and normal.  Dysregulation of cell death probably equals cancer.

P:  Could a cell that mutates, but does not die in apoptosis, become cancerous?  I mean, in general, in the body. 

Dr. Jeff Henderer:  Probably, yes.  That's why anti-apoptosis medications have to walk a fine line.  You don't want to prevent glaucoma and stimulate other problems.

P:  My doctor has recommended taking ginkgo biloba, 120 mg, twice a day.  What do you think? 

Dr. Jeff Henderer:  Ginkgo does help blood flow, and if that can help glaucoma, it might be beneficial.  Unless you are also taking aspirin, it is probably safe.

P:  Would you suggest taking ginkgo biloba?   

Dr. Jeff Henderer:  Usually I only recommend ginkgo if nothing else seems to be working, or the patient seems to have a good IOP, but feels he or she is getting worse.  There is probably no reason not to take it, though, unless you are already on aspirin.

P:  How much aspirin?

Dr. Jeff Henderer:  Probably what you would take for heart disease, 81 mg a day. But there is no evidence that aspirin helps glaucoma.

P:  You wouldn't recommend taking ginkgo and aspirin because aspirin also thins the blood?  

Dr. Jeff Henderer:  Yes. 

P:  I understand that there are medications in the works that will specifically affect neuroprotection.  Is that correct?  Are we likely to see some soon?

Dr. Jeff Henderer:  There is a drug in clinical trials called memantine that might be promising.  It is an anti-Parkinson medication.  Might be a couple more years, though, before we see it in use.  

P:  Programmed cell death?  Suicide?  Sorry, I missed this entirely.  What is apoptosis?  That's probably not the topic tonight. 

Dr. Jeff Henderer:  It is a normal means of the body cleaning house to eliminate old cells.  Apoptosis is a normal process in development.  The details were first worked out in flatworms, so you know that this process has been around for millions and millions of years.

P:  If the nerve is damaged from a disease that is not glaucoma, would Betoptic keep it from getting worse?

Dr. Jeff Henderer:  That is a great question.  There's no evidence of that, but believe me, the neurologists are interested in that!

P:  How does blood flow figure into neuroprotection?

Dr. Jeff Henderer:  The more oxygen, the fewer free radicals and ischemia, both of which can trigger apoptosis -- which really is the topic tonight.  

P:  So, does increased blood flow mean more oxygen or less?

Dr. Jeff Henderer:  More.  Let me explain the process a bit.  Apoptosis is programmed cell death, meaning that within each cell in our body there are some proteins that want to keep the cell alive and some that want to kill the cell.  The balance of the two forces determines if the cell lives. If an external (or internal) trigger tips the balance to cell death, then a set of enzymes takes over and kills the cell.

P:  Is the topic tonight glaucoma or apoptosis?

Dr. Jeff Henderer:  Both.  Glaucoma probably is due, at least in part, to apoptosis. That is the mechanism of  the actual damage to the eye.  Now, what causes it -- high IOP, poor blood flow, genetic defect, or other?  That is the million-dollar question.

P:  Wow!  I never heard of that before tonight.  Thank you.  Docs are always so focused on pressures when we are first being treated.

Dr. Jeff Henderer:  Remember, there has to be a reason that the nerve dies in glaucoma.  We don't know what it is.  We do know IOP plays a big role.  But how does IOP kill the nerve?  That is where apoptosis fits in.

Monitor:  In an article I read some time ago, Dr. Alon Harris at Indiana University said he thinks the carbonic anhydrase inhibitors show the most promise for blood flow -- dorzolamide, brinzolamide and timolol-dorzolamide.  Recently, one of our group consulted Dr. Harris.  I wonder if the doctor mentioned that to him. 

P:  Yes, in fact, we are testing that now on my glaucomic eyes.

Monitor:  Are other glaucoma patients involved in the test? 

P:  He does not have a full study -- just me.  Also, I have volunteered to help them develop a new unit that measures oxygen in the vascular system of the eye.

P:  Dr. Jeff, is there any evidence that any of the commonly used drops inhibit neuroprotection (even if they also lower IOP)?  Sorry for the scary question!

Dr. Jeff Henderer:  Not that I know of.

P:  Is it possible or probable that timolol can lower low-normal blood pressure in some patients so that blood flow to the optic nerve is reduced, especially at night, to the point of causing a stroke to the optic nerve?

Dr. Jeff Henderer:  Yes, that is a potential big problem.

P:  Doctor, you do a fantastic job answering our questions.  We really cram a lot into our sessions with you!

Dr. Jeff Henderer:  You guys had great questions tonight!  Excellent!

P:  Doctor Jeff, where is your office?

Dr. Jeff Henderer:  I am in Wilmington, Delaware; Marlton, New Jersey; Bala Cynwyd, Pennsylvania; and at Wills in Philadelphia, Pennsylvania. 

Moderator:  Thanks for answering all our questions.  

Dr. Jeff Henderer:  Thank you all! Great to talk to you.

End of highlights for October 10, 2001.

On October 17, Dr. Wilson discussed "Glaucoma Medications" in the Chat room. Click here for highlights of that meeting.

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