Health & Medicine - Posted by Jerry Jones-Vanderbilt on Monday, March 8, 2010 12:05 - 12 Comments 
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(4 votes, average: 5.00 out of 5) Loading ...Glaucoma’s blindness starts in the brain
“If you followed the disease long enough, eventually the optic nerve, then the retina, show signs of degeneration,” explains David Calkins (above). “So the degeneration works in reverse order. It starts in the brain and works its way back to the retina so that in the very latest stages of the disease, the earliest structures, the ones nearest the eye, are the last to go.” (Credit: Joe Howell)
VANDERBILT (US)—The first sign of injury in glaucoma occurs in the brain, not the eye as previously thought. A new study shows glaucoma is very much like other central nervous system diseases.
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“This is a paradigm shift on how we think about this disease,” says David Calkins, associate professor of ophthalmology at Vanderbilt University and director of research at the Vanderbilt Eye Institute (VEI). “This will have global implications. This information opens up an entirely new domain of nerve-derived therapeutics.”
Combining this new understanding of where the first neuronal injury for glaucoma occurs, with the fact that the incidence of injury increases with age, researchers now have insight into how the loss of sensory function occurs in normal aging. Findings are reported in the Proceedings of the National Academy of Sciences.
Glaucoma is generally considered a disease of the eye in which sensitivity to ocular pressure causes damage to the retina and optic nerve, which are components of the central nervous system and do not regenerate.
The damage begins in the peripheral visual field and progresses toward the center resulting in complete blindness unless detected early. For this reason, degeneration in glaucoma is often hard to detect.
Traditionally, glaucoma therapies have focused on lowering ocular pressure within the eye. But recent developments give credence to taking a new direction of study focusing on neuronal activity in the middle of the brain where the optic nerve forms its first connections.
“This is very exciting work that demonstrates that we must consider not just the eye, but also the brain, in our efforts to understand blinding diseases such as glaucoma,” says Paul Sternberg, chair of Ophthalmology and Visual Sciences and director of VEI.
“We are optimistic that Dr. Calkins’ neurobiological approach will lead to new targets for potential treatment of this devastating condition.”
Calkins explains that in other age-related diseases, like Alzheimer’s and Parkinson’s, the most significant contributor to neuronal susceptibility to injury is age.
“In these diseases, the injury to neurons occurs very early in the distal projections in a process called dying back. In dying back, the neuronal axon loses its ability to communicate with the target.
“In the case of glaucoma, we have showed that the axons in the optic nerve lose their ability to communicate with their projection site in the mid-brain.”
Calkins’ team expected to find a loss of communication in the optic nerve of the eye, but what they also discovered was that the connectivity between the optic nerve and the brain was dying first.
Using animal models with high pressure glaucoma, the team was able to see that a very early mechanism of vision loss involves the loss of communication between the optic nerve and the mid-brain, where sensory information about sound, heat, cold, pain and pressure originate.
“If you followed the disease long enough, eventually the optic nerve, then the retina, show signs of degeneration,” explains Calkins.
“So the degeneration works in reverse order. It starts in the brain and works its way back to the retina so that in the very latest stages of the disease, the earliest structures, the ones nearest the eye, are the last to go.”
Now the team is working on finding drugs that can improve or restore the connectivity between the optic nerve and the mid-brain. Using both synthetic compounds and natural nerve growth factors such as brain-derived neurotrophic factor (BDNF), the team is examining how to restore communication in the pathway.
According to National Eye Institute projections, by the year 2020, 80 million people worldwide will have glaucoma. The risk of vision loss in glaucoma cases increases sevenfold after the age of 55.
“People really thought we were crazy when we first suggested that the first signs of injury for glaucoma were in the brain,” he says. “What this discovery does is to allow us to view this disease through the same lens that we view other age-related neurodegenerative disorders.”
The study, which also introduces the possibility of using MRI scans as an early diagnostic tool, was funded by the Glaucoma Research Foundation, Research to Prevent Blindness and the National Eye Institute.
Vanderbilt University news: www.vanderbilt.edu/news
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12 Comments
George
George,
Current treatments for glaucoma that reduce eye pressure do slow the progress of the disease. If started early enough they are effective to the point of allowing a patient to maintain effective sight for life. This new insight (pun intended) shows how to get to the cause rather then the effect.
Hello!
I am happy to hear the progress in the Glaucoma research. I have Tinnitus, rining in the ears, head noises….. I do feel at times is related with my Glaucoma. I feel like a little vibration in the middle of my head. Brain, at times. When I was first diagnosed with it. I thought it was going to be the end of me. the doctor told me as you get older you lose brain cells. I know when I got it. I was listening to dictation from a tape from psychologist dictating and I was having difficulty listening to it so I raised the volume loud many times, thinking I was going to hear better. At one point doing that I developed a tight belt around my head, and terrible headache.After thet the hight pitch distrating begaun to sound. Ever since I’ve had it. I am letting you knoe of my experience. When I go under the shower it deminishes. If I get upset/and/or anxious it exacerbates. It is usually high but it can go low but not for a long time. It is depressive, for I have no piece of mine and it is distracting too. I hope that finally they can come up with a cure or at least making this nice to go lower….
Marina Bosi
Thank you so much dear professor! I have always thought that glaucoma is a neurodegenerative disease detectable monitoring the optic disk of our patients. A disregulation in the mid brain is responsible of a cascade of effects that determine also the optic nerve head glaucomatous atrophy. I agree with you.
Please help me. Why the glaucomatous atrophy of the optic nerve is typical only of glaucoma? Why the progression of glaucoma is different in different patients? Is possible to detect distrophies and atrophies also in the primary occipital visual cortex in glaucomatous patients ? Why? Why is it not possible to see the typical glaucomatous atrophy in different diseases of the brain like in Alhzeimer and Parkinson?Is it because the first site of these diseases is not in the midbrain? I would like to know more. Congratulation! This new way of thinking Is like a Galileian revolution.
Test
Testy
Irene
Hello!
I am happy to hear the progress in the Glaucoma research. I have Tinnitus. The ringing in the ears, head noises. At times, I feel it is related with my Glaucoma. I feel like a vibration in the mid part of my head. It feels it comes from my Brain. When I first was diagnosed with Tinnitus.. I thought it was going to be the end of me. My ENT., doctor told me . . . as we get older we lose brain cells. I know when I got it. I was transcribing from dictation. Many times I raised the volume thinking I could hear better. I was having difficulty listening to it so I kept raising the volume higher and higher. At one point I felt I had a belt, tightening wrapped around my head. And a terrible headache developed. .After that I begun to hear the high pitch sounds, distrating ttoo. Ever since then I’ve had it. I am letting you know of my experience with Tinnitus. I think it is all related… When I go under the shower , the sounds deminishes for a litle while. If I get upset/and/or anxious / it exacerbates also. It is usually high but it can go low but not for a long time. It is depressing. I cannot get rid off of it… I hope that finally they can come up with a cure or at least making this noise get lower or go completely away! I’ve thought that it could be related with my Glaucoma. Fixed typographical errors.
I do not think glaucoma starts in the midbrain. Pathognomonic feature of chronic glaucoma are arcuate field defects in early stages of glaucoma. Arcuate axons lie above and below the macular fibers in the retina. Arcuate field defects are perhaps the only lead we have in finding the pathogenesis of glaucoma. Can the injury starting in the midbrain selectively destroy the arcuate fibers in the initial stages of glaucoma? I think it will be unlikely.
I hypothesize that the primary pathology of glaucoma lies in the border tissue of Elschnig and not in Lamina cribrosa. Circular border tissue keeps the optic disc in place in the scleral canal as a ‘O” ring seal. Border tissue atrophies due to chronic ischemia either due to high intraocular pressure or due to poor systemic cardio-pulmonary and circulatory problems. Due to atrophy of the border tissue the optic disc will start sinking in its entirety. Due to normally temporally tilted disc the temporal fibers consisting of superior and inferior arcuate and centrally located macular fibers will be stretched and severed against the scleral edge due to sinking disc earlier. Arcuate fibers being fewer in number compared to the macular will be depleted earlier giving rise to arcuate field defects.
Sinking of the optic disc and severing of the axons are unique to glaucoma. Axotomy of the axons results in excavation of the disc which is characteristic of glaucoma unlike flat disc atrophy in which the axons are atrophied but not severed therefore no excavation of the disc in such cases. Sinking of the disc will become unstoppable akin to a sinking ship. Due to severance of the axons there will be retrograde degeneration of the ganglion cells of retina proximally and in the neurons in the LGN in midbrain and in the occipital cortex distally. i believe the primary pathology lies in border tissue around the optic disc and not in the midbrain. If the pathology at the level of midbrain can cause selective destruction of the arcuate fibers in the intial stages of glaucoma then it will be a interesting phenomenon.
My brother has mild cerebral palsy (5%), he’s 44 years old. When he was in his mid 30′s he began getting eye drops because they noticed early stage glaucoma. We assumed it was hereditary because our great grandmother and her 2 sons had it.
Any thoughts on glaucoma being hereditary?
Are his chances increased because of the effects of cerebral palsy?
Why does it occur more in African Americans? (Think I read that stat before.)
There have been so certain hypotheses about Glaucoma. It has been said that Glaucoma is because of cupping. If that had been the case, why as of today there has not been any treatment for it. Dr. Syed Hasnain says its due to sinking and does make sense. Why not go ahead and open the door for further research on the hypothesis that Dr. Hasnain has come up with. If Dr. Hasnain is right then we can see many Glaucoma patients with a hope and start looking for cure of Glaucoma. More than 150 years passed by and as of today we are following the theory of cupping which has not taken us any where. I insist that most of the researchers should consider Dr. Hasnain’s idea of Sinking and find a cure of Glaucoma. If he is right, then many people in this world will benefit from it.
pathogenesis and treat glaucoma
Dear colleague, my name is Evgeny Emelyanov.
I would like test new hypothesis of pathogenesis and treat glaucoma, which can give new
sight to a problem (save nerve optical, save vision). I don’t found in all sources of information
about study glaucoma the line of investigation like my. Now I try find university or center for experiment.
Can I offer to you test jointly my hypothesis?
If it will truth I really ready pass all rights to investigator.
Yours faithfully , Evgeny Emelyanov
june
Hi. My mom of 90 was diagnosed with glaucome and cataracts. The standard treatment of eye drops was prescribed and she attended the free clinic every 6 months. They decided to do a cataract op on the good eye to restore more sight. This failed dismally and she was blind from then on. She is now unable to walk and I cannot get her to the free clinic anymore. She gets two kinds of drops morning and evening plus a third one in the evening. The cost of the drops alone takes her whole pension for the month. As she is now totally blind, does she still need to use the drops or is there an alternative item that is not so expensive that she can use. Thank you
June
I’m in my early 40′s, and have recently been warned by my ophthalmologist that my intra-ocular pressure is raised, and I need to have it checked regularly. My mother has the early stages of glaucoma, and suffers from hearing loss and dementia. I’ve shared several of her other health problems including hypothyroidism, and migraines characterized by photo-sensitivity and aura. Recently I’ve developed annoying, frequent tinnitus that is worsened by stress. I share my concern with Irene, that the recent bouts with tinnitus seem to be related to increases in intra-ocular pressure, and it could be a warning sign of glaucoma. I believe it’s worth a study.
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Does this mean then that the treatment(s) to reduce the eye pressure have not effect on halting the onset, indeed, the progress of glaucoma?