Glaucoma refers to increased pressure within the eye (intraocular), which results from greater production than outflow of the fluid of the eye (the aqueous humor). The normal intraocular pressure is about 10 to 21 mm Hg. In chronic glaucoma, the intraocular pressure is usually mildly to moderately elevated (22 to 40 mm Hg). In acute glaucoma, the intraocular pressure is greater than 40 mm Hg.
ACUTE GLAUCOMA
*Increased pressure within the eye (intraocular), usually on one side only
*Severe throbbing pain in eye with markedly blurred vision
*Pupil moderately dilated and fixed
*Nausea and vomiting is common
CHRONIC GLAUCOMA
*Persistent elevation of the pressure within the eye (increased intraocular pressure)
*Usually no symptoms are apparent in the early stages
*Gradual loss of peripheral vision resulting in tunnel vision
In the United States, there are approximately two million people with glaucoma, twenty-five percent of which is undetected. Ninety percent is of the chronic type. Nearly two percent of people over the age of forty have glaucoma, and by age seventy over ten percent have glaucoma. Glaucoma is a major cause of blindness in adults.
The cause of glaucoma appears to be an abnormality in the composition of the supportive structures of the eye. Specifically, biopsy samples indicate that there is a strong correlation between the content and composition of collagen and that of the glaucomatous eye. Collagen is the most abundant protein in the body, including the eye. In the eye, it provides support and integrity to all eye structures, based on what the professionals say, Collagen is vital for your eyes. Inborn errors of collagen metabolism (e.g., osteogenesis imperfecta, Ehlers-Danlos syndrome, Marfan’s syndrome) are often associated with eye disorders such as glaucoma and retinal detachment. Structural changes reflecting poor collagen integrity and function are the hallmark features of glaucoma. These changes lead to blockage in the flow of the aqueous humor and result in elevated intraocular pressure (TOP) readings and can lead to the progression of peripheral vision loss.
Glaucoma is a leading cause of blindness throughout the world, affecting over 60 million people. Glaucoma is an optic neuropathy in which the pressure within the eye becomes elevated due to blockage of the normal flow of fluid between the cornea and lens. In the course of the disease, axons of the optic nerve die and the plates of lamina cribosa collapse leading to deterioration of the optic nerve tissue. When axonal deterioration progresses to a certain point, peripheral vision begins to decline, with central vision becoming affected much later.
Glaucoma may also be classified as two main types: (1) primary, open-angle glaucoma (POAG) is the most common form in whites and blacks with incidence increasing with age; (2) angle-closure glaucoma is more widespread in the Far East, primarily China.
Primary Open-Angle Glaucoma
In POAG, intraocular pressure (I0P) rises slowly and painlessly, often going undetected until the later stages. Watery fluid known as aqueous humor constantly circulates through the anterior chamber of the eye, flowing between the iris and the lens. The trabecular meshwork, serving as a drain, is located in the angle where the iris and cornea meet. When the trabecular meshwork becomes clogged, the aqueous humor cannot drain, causing fluid to back up, which in turn causes pressure to build up within the eye. The fluid is forced out of the weakest part of the eye, the sclera, where the optic nerve leaves the eye. The extremely thin optic nerve cells become compressed, damaged, and eventually die. This results in permanent vision loss.
Symptoms of POAG are a progressive loss of peripheral vision, blurred vision, tearing watery eyes, and occasional headache. POAG is primarily a diagnosis of exclusion, indicating that upon examination, it cannot be identified as another specific disorder. Specialists often believe it is idiopathic in nature and there are various theories concerning the cause of elevated IOP These include abnormal cell function in the trabecular meshwork, fewer cells in the trabecular meshwork due to aging, a structural defect in the eye’s drainage system, or an enzymatic abnormality. -Juvenile POAG presents by the age of 35 and is most often a familial disorder. Researchers have localized the gene in a number of families on the short arm of chromosome. This gene has been identified as producing a protein that affects the “”stickiness”” of the fluid pathways in the trabecular meshwork.
Angle-Closure Glaucoma
Angle-closure glaucoma has a familial tendency and is also more common in farsighted individuals. Individuals with angle-closure glaucoma have a narrower than normal angle in which the trabecular meshwork and iris are located. Upon aging, the lens grows larger and the ability of aqueous humour to pass between the iris and lens while flowing into the anterior chamber becomes decreased. This causes a fluid buildup and narrows the angle even more. When the space between the iris and the trabecular meshwork becomes completely blocked, an acute angle-closure glaucoma attack ensues. An acute attack will be characterized by severe, sudden eye pain, blurred vision, nausea, headaches, and rainbow-like halos around lights.
Treatment
Glaucoma must be diagnosed and treated early to prevent further degeneration of eyesight. Using a simple procedure called tonometry, an ophthalmologist or optometrist will measure fluid pressure in the anterior chamber of the eye. To reduce IOP, the amount of aqueous humor must be decreased or the outflow through the trabecular meshwork must be increased. Treatment usually begins conservatively with a long-term topical drug (eye drops) such as a beta-adrenergic antagonist. If needed, other treatments may be given either topically or systemically. These include prostaglandin analogs, adrenergic agonists, carbonic anhydrous inhibitors, and cholinergic agonists. Patients must be monitored closely for pulmonary and cardiac side effects. When drugs are no longer effective in keeping IOP under control or when new or worsening optic nerve damage occurs, treatment will be intensified. Laser surgery may be used if appropriate, to unblock clogged drainage channels or to surgically create a new pathway for the outflow of aqueous humor.
New Approaches to Understanding Glaucoma
New research in the field is leading specialists to consider non pressure-related factors in the treatment of glaucoma. While IOP is the most important risk factor, other related conditions are being discovered as well. Researchers are studying a pigment dispersion syndrome in which the iris rubs against the zonules, which hold the lens in place, causing disruption of the pigmented cells in the back of the iris and releasing pigment, which clogs the trabecular meshwork. Uveitis, in which inflammation gradually kills off the trabecular cells, may also play a role. Further research on inflammation and the immune system is needed to treat the effects of uveitis.
Abnormal or insufficient blood flow to the optic nerve head and retina is also under investigation as a risk factor for glaucomatous damage. Other hemorheologic factors may include increased erythrocyte agglutinability, increased serum viscosity, and decreased erythrocyte deformability. Other possible risk factors include low blood pressure, abnormal (inherited or acquired) connective tissue of the lamina cribosa, low intracranial pressure, primary ganglion cell degeneration, and the effect of excitotoxins such as aspartate (Nutrasweet) and glutamate.
A recent study reported in the Proceedings of the National Academy of Sciences that the drug aminoguanidine may help save the vision of patients with hard-to-treat glaucoma by inhibiting buildup of NOS-2. Researchers studied the effects of nitric oxide synthase 2 (NOS-2), an enzyme that appears to collect on the optic nerves of glaucoma patients. NOS-2 stimulates the emission of nitric oxide, a compound implicated in the retinal nerve damage associated with glaucoma. Researchers testing the effectiveness of aminoguanidine on rats with raised IOP over a 6-month period reported that no cupping of the optic disk occurred in those rats treated with aminoguanidine compared with rats left untreated. Intraocular pressure remained elevated throughout the study-whether animals received aminoguanidine or not. According to researchers: “”That is important, because it means that lowering the pressure is not what protected the retina.”” Researchers concluded that this is an important finding for those ‘hard-to-treat’ patients who do not respond to traditional therapies.””
The Beneflts of Nutritional Supplementation
Maintaining collagen integrity can play an important role in both treatment and prevention of glaucoma. Vitamin C and MSM are known to improve the condition of collagen structure throughout the body. In clinical studies, it has also reduced IOP levels in some patients who were unresponsive to standard glaucoma drugs. Dosage may be administered orally or intravenously and patients must be monitored to achieve optimal dosing benefits. Intravenous administration is the most effective means of reducing IOP, but must be done on a continued basis. MSM eye drops used 3 to 5 times daily is also effective in draining the eye.
Bioflavonoids also aid collagen metaboeÿu. These compounds have been shown to improve capillary integrity, prevent free-radical damage, and inhibit cross-linking with collagen fibers to form a more stable collagen matrix. European bilberry (Vaccinium myrtillus), an anthocyanoside, has been used in Europe for a variety of eye problems, with very good results. Rutin, a citrus bioflavonoid, has been used successfully as an adjunct to lower IOP Subclinical hypothyroidism (see Thyroid Deficiency protocol) should be evaluated and treated if found to further lower intraocular pressure.
Ginkgo biloba extracts, standardized to 24% ginkgo flavonglysides, demonstrated some improvement in reducing IOP and improving visual field in glaucoma patients at dosages of 160 mg a day for 4 weeks and then 120 mg a day thereafter. Although only mild improvements were seen, the severity of the condition deemed the results relevant.
The effects of magnesium are similar to those of drugs used as “”channel blockers”” in the treatment of glaucoma. Channel blockers block the entry of calcium to produce relaxation of the arteries. Glaucoma patients given magnesium at a dose of 121.5 mg twice a day for 4 weeks showed improvement in blood supply and visual field due to the effects of relaxing constricted blood vessels.
Other dietary supplements shown to contribute to a reduction in IOP are chromium and omega-3 oils. Chromium aids in the ability of eye muscles to focus. In a study of 400 eye patients, deficiencies in either vitamin C or chromium were associated with elevated IOP In animal studies, cod liver oil was shown to significantly reduce IOP when administered orally or intramuscularly. When removed from dosing, IOP levels returned to baseline.
CHROMIUM
Chromium is a glucose-uptake insulin-reccptor potentiator, which is thought to enable sustained strong ciliary-muscle eye-focusing activity. A deficiency is associated with elevated intraocular pressure, which tends to stretch the eye to reduce the need for focusing power (Lane).
Primary open-angle glaucoma appears to be strongly associated with erythrocyte chromium deficiency. In fact, the most significant biochemical differcntiator between normals and persons with primary open-angle glaucoma is erythrocyte chromium (Lane).
Based on informal clinical observations, patients who are likely to respond to chromium repletion are likely to have undrugged intraocular pressures of more than 20 mm Hg as well as erythrocyte chromium levels of no more than 150 ng/ml (Lane). These observations need confirmation with formal controlled trials.
LIPOIC ACID
Levels of the antioxidant glutathione have been found to be low in lacrimal fluid (Fifina, 1993), anterior chamber humor, and red cells (Bunin) in patients with chronic open-angle glaucoma.
Based on measurements in lacrimal fluid, supplementation with alpha-lipoic acid appears to be an effective means of providing antioxidant therapy of chronic open-angle glaucoma by increasing glutathione levels (Fifina, 1993). Moreover, in a controlled study, supplementation improved visual function in patients with stage I or II open-angle glaucoma (Filina, 1995).
Hydergine, a prescription drug, enhances energy cycles in the eye that are necessary to move aqueous humor into and out of the eye . A dose of 5 to 20 mg a day of Hydergine could be effective in lowering intraocular pressure. It is mandatory that you have regular intraocular pressure tests administered by an ophthalmologist if you are trying to use Hydergine as a treatment for glaucoma.
Supplemental thiamine should be considered by the glaucoma patient as well. In two separate studies conducted in the U.S. and Russia, glaucomatous patients were found to have significantly lower thiamine levels than controls. Thiamine, in daily dosages of up to 20 mg, was administered both parenterally and orally with improvement of visual functions observed between days 2 and 6. As stated earlier, aminoguanidine may help save the vision of patients with hard-to-treat glaucoma, according to the August 17, 1999 issue of the Proceedings of the National Academy of Sciences (1999; 96:9944-48). This study showed that only 10% of crucial vision cells in the retina were lost in a group of aminoguanidine-supplemented rats compared to a 36% loss of retinal cells in the group not receiving aminoguanidine. The study was funded by the National Eye Institute and the Glaucoma Foundation. Dr. Robert Ritch, chair of the Foundation’s scientific advisory board, said, “”Although the current investigations do not yet translate into clinical use, this [study] is the sort of breakthrough research that could eventually lead to a stemming of vision loss from glaucoma.”” The recommended safe dose of aminoguanidine is 300 mg a day. Aminoguanidine is especially important for diabetics, who suffer from greatly accelerated glycosylation throughout their body. It appears that the glycosylation mechanism of damage is responsible for vision problems caused by cataracts and glaucoma.
For more information, Contact the Glaucoma Research Foundation, (800) 826-6693.
1. Pre-Disposing Factors:
a. Atherosclerosis.
b. Zinc, vitamin B-6, vitamin A or vitamin C/bioflavinoid, Sulfur deficiency.
c. Food/environmental sensitivity.
d. Genetic pre-disposition.
e. Diets deficient in antioxidants.
f. Poor calcium metabolism resulting in carbonate formation.
2. Dietary Suggestions:
a. Eliminate all refined carbohydrates, alcohol and especially caffeine containing foods such as coffee, colas chocolate and tea.
b. Eliminate hydrogenated fats and oils such as margarine. Eat only coconut oil, extra virgin olive oil and fish oils as your only source of dietary oils.
c. Sip 1 mouthful of filtered water every 30 minutes while awake. Avoid the ingestion of large amounts of fluids in a short period of time that can increase the aqueous fluid production and cause increased IOP.
d. Avoid iron cooking utensils and iron-containing supplements.
e. Increase the use of fresh raw fruits and vegetables and quality protein like cold-water at e such as mackerel, herring haddock and salmon, which are high in the Omega-3 fatty acids.
GENERAL SUPPLEMENT PROGRAM
General Nutrients:
1. IRON FREE BIO-MULTI PLUS — 1 tablet, 3 times daily after each meal
2. BIO-C PLUS 1000 — 1 tablet, 4 times daily after each meal and at bedtime
3. M S M POWDER — 1/2 teaspoonful, 4 times daily depending on the severity of symptoms. NOTE: Try to take your Vitamin C with your MSM.
NOTE: Take M S M 2 to 4 times daily until all symptoms resolve, then decrease dosage to once or twice daily or whatever you feel your optimum dose is.
4. BIOMEGA-3 — 4 capsules daily after a meal
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SPECIFIC NUTRIENTS (Use for 1 month, then re-evaluate)
5. OPTIC PLUS — 2 tablets, 3 times daily after meals.
6. BIO-PROTECT — 2 capsules, 3 times daily after meals.
7. GINKO BILOBA ? 1 tablet, 4 times daily after meals and at bedtime for 1 month, then 1 tablet, 3 times daily after meals thereafter
8. LIPOIC ACID – 2 capsules, twice daily after meals
9. CR-ZYME ? 1 tablet, twice daily after meals
ALSO CONSIDER:
10. HYDERGINE 5mg ?- 1 tablet 2 to 3 times daily after meals.
11. AMINOGUANIDINE ? 300mg per day
Specific Nutrients: When symptoms or condition begins to subside, gradually, as needed, wean yourself from the Specific Nutrients & stay on the Primary Nutrients. If any symptoms re-occur resume taking Specific Nutrients.
NOTE: Look up the appropriate supplement in the PRODUCTS FOR HEALTH section of this web site for more information about that product before you decide to order (if you need to) under the section PRODUCTS FOR ORDERING.
ADDENDUM
Study suggests potential new approach to glaucoma therapy
St. Louis, Aug. 17, 1999 — Investigators at Washington University School of Medicine in St. Louis believe they have identified the basis for a new way to treat glaucoma, the second-leading cause of irreversible vision loss in the United States.
In the Aug. 17 issue of Proceedings of the National Academy of Sciences, the investigators report on experiments involving an animal model of glaucoma. Working in rats with elevated eye pressure, they were able to prevent loss of retinal ganglion cells by inhibiting the action of an enzyme that makes nitric oxide.
“”Having seen reports on nerve damage caused by excessive nitric oxide, we decided to look for evidence of high levels of nitric oxide in human eyes with glaucoma,”” said lead author Arthur H. Neufeld, Ph.D., the Bernard Becker Research Professor of Ophthalmology and Visual Sciences. “”Using sophisticated staining techniques, we detected an enzyme called inducible nitric oxide synthase in the optic nerve head tissue of patients with glaucoma.””
This enzyme – NOS-2 – can produce excessive amounts of nitric oxide, and Neufeld and colleagues regarded its presence as evidence that nitric oxide might be involved with the ganglion cell damage seen in glaucoma. To explore that idea, they set out to determine whether NOS-2 was causing the damage in retinal cells or appearing as a byproduct of that damage.
“”We adopted an animal model of glaucoma that raises pressure levels in the eyes of rats,”” Neufeld said. “”And we found that, as in humans, the eyes of rats with elevated pressure lost retinal ganglion cells and that the tissue also contained elevated levels of NOS-2.””
For the last century, most medical and surgical therapies for glaucoma have attempted to lower pressure in the eye, aiming to prevent or delay damage to ganglion cells and preserve good vision. “”But we have many clinical situations where we can’t get the pressure low enough to avoid damage,”” said Bernard Becker, M.D., professor emeritus and former head of the Department of Ophthalmology and Visual Sciences. “”In spite of the drugs we have, in spite of surgery, in spite of everything we try to do, the patient continues to lose vision.””
Inhibiting NOS-2 may provide a new option. The investigators put a drug called aminoguanidine into the drinking water of rats with elevated eye pressure. Other rats did not get the drug. After six months, the researchers found that the untreated rats lost 36 percent of their retinal ganglion cells in the eyes with elevated intraocular pressure. Those who received aminoguractine lost less than 10 percent of their retinal ganglion cells in spite of continued elevated intraocular pressure.
“”As the paper reports, there were marked changes in the eyes of animals that did not receive the drug,”” Neufeld said. “”But we didn’t seen that type of cell loss in animals that were treated with aminoguanidine. Statistically, the retinal ganglion cell loss was not any different than in the controls.””
Processes from retinal ganglion cells leave the eye through a structure called the optic disc, and ophthalmologists keep a close watch on the optic disc in glaucoma patients. In this study, Becker did the same thing with the rats.
“”Once a month, we looked into the animal eyes through an ophthalmoscope,”” he explained. “”Patients with glaucoma develop ?cupping? of the disc – a bowing back and atrophy of that structure. These rats also were developing this cupping of the optic disc, but in those treated with aminoguanidine, no cupping occurred.””
Although the rats treated with aminoguanidine had less damage in the retina and the optic nerve, their intraocular pressure was no different than in animals that did not receive the drug. “”That means aminoguanidine did not lower the elevated pressure in these animals,”” Neufeld said. “”That is important because it means that lowering the pressure is not what protected the retinal ganglion cells.””
That fact gives the researchers hope that it may be possible to treat patients whose glaucoma does not respond to pressure-lowering drugs or surgery, as well as a subset of patients who have what doctors call normal-pressure glaucoma. The hope is inhibitors of NOS-2 might preserve vision in those patients who don’t respond to current therapies and also could be used along with drugs that lower intraocular pressure.
“”The emerging concept of using drugs to protect nerve cells is being aggressively pursued across the country,”” said Carl Kupfer, M.D., director of the National Eye Institute, part of the National Institutes of Health, the federal agency that helped fund the study. “”New approaches to treating glaucoma are welcome, and this work will be followed closely by other glaucoma researchers.””
Robert Ritch , M.D., agrees. He is chairman of the scientific advisory board of The Glaucoma Foundation, which also helped fund this project. “”We?re getting closer to finding the answers,”” Ritch said. “”Although the current investigations do not yet translate into clinical use, this is the sort of breakthrough research that could eventually lead to a stemming of vision loss from glaucoma.””
In an accompanying commentary article, Paul L. Kaufman. M.D., professor and Director of Glaucoma Services at the University of Wisconsin-Madison, said the paper “”will likely be considered a classic in years to come”” and that the study’s conclusions may contribute to more than finding better treatments for glaucoma. “”The significance of their findings may go far beyond glaucoma, with broad pathophysiologic and therapeutic implications for neurodegenerative and neurovascular diseases in general,”” Kaufman wrote.
For now, however, the research is focusing purely on glaucoma. In future animal studies, Neufeld and Becker will test other drugs that inhibit production of NOS-2. If their work progresses, human trials may follow.
This research was supported by grants from the National Eye Institute and the Glaucoma Foundation.
Neufeld AH, Sawada A, Becker B. Inhibition of Nitric Oxide Synthase-2 by Aminoguanidine Provides Neuroprotection of Retinal Ganglion Cells in a Rat Model of Chronic Glaucoma. Proceedings of the National Academy of Sciences, vol. 96 (17), pp 9944-9948, Aug. 17, 1999.
Copies of the paper are available from the PNAS news office, (202) 334-2138, or email <pnasnews@nas.edu>.
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NO to Glaucoma
By Sean Henahan, Access Excellence
St. Louis, MO (8.19.99)- A new neuroprotective approach aimed at blocking the synthesis of nitric oxide (NO) may offer the hope of new treatments for glaucoma, a leading cause of blindness in the world.
The gradual vision loss seen with glaucoma is associated with a progressive loss of retinal ganglion cells and axons leading to deterioration of the optic nerve. Elevated intraocular pressure (IOP) has been a known risk factor for glaucoma for at least a hundred years, and all current treatments aim to lower IOP as a means to slow the progression of disease.
While these pressure-lowering approaches have been shown to provide significant benefit, none are curative. Some patients develop glaucoma in the absence of elevated intraocular pressure, and others fail to show much improvement even when the pressures are reduced. Researchers have only very recently begun to explore the role that various neurochemicals play in the glaucoma disease process. While the optic nerve is best known for carrying visual signals from the retina to the brain, it also carries many other things including include mRNA, proteins and amino acids.
Of particular interest are neurotrophins, peptides that interact with cell surface receptors to moderate cell growth and stasis. As glaucoma develops, the flow of neurotrophins to the retinal cells is impaired. This is part of larger cascade of events associated with elevated IOP. Other factors include ischemia, vascular dysfunction and the release of cytotoxins including glutamate. The goal of neuroprotection therapy is to interrupt this process at one or more stages.
New research conducted at the Washington University School of Medicine indicates that excess nitric oxide, a ubiquitous chemical in the human body, is associated with increases in IOP and other signs of glaucoma in animal models. They also determined that administering a drug that inhibits the synthesis of NO appear to prevent or delay the progression of the disease.
“”Having seen reports on nerve damage caused by excessive nitric oxide, we decided to look for evidence of high levels of nitric oxide in human eyes with glaucoma. Using sophisticated staining techniques, we detected an enzyme called inducible nitric oxide synthase in the optic nerve head tissue of patients with glaucoma,”” said Arthur H. Neufeld, Ph.D., the Bernard Becker Research Professor of Ophthalmology and Visual Sciences,Washington University School of Medicine
This enzyme, NOS-2, can produce excessive amounts of nitric oxide. Neufeld and colleagues regarded its presence as evidence that nitric oxide might be involved with the ganglion cell damage seen in glaucoma. To explore that idea, they set out to determine whether NOS-2 was causing the damage in retinal cells or appearing as a byproduct of that damage.
“”We adopted an animal model of glaucoma that raises pressure levels in the eyes of rats. And we found that, as in humans, the eyes of rats with elevated pressure lost retinal ganglion cells and that the tissue also contained elevated levels of NOS-2,”” Neufeld said.
Next, the investigators put a drug called aminoguanidine into the drinking water of rats with elevated eye pressure. Other rats did not get the drug. After six months, the researchers found that the untreated rats lost 36 percent of their retinal ganglion cells in the eyes with elevated intraocular pressure. Those who received aminoguanidine lost less than 10 percent of their retinal ganglion cells in spite of continued elevated intraocular pressure.
“”There were marked changes in the eyes of animals that did not receive the drug. But we didn’t seen that type of cell loss in animals that were treated with aminoguanidine. Statistically, the retinal ganglion cell loss was not may different than in the controls,”” Neufeld said.
Interestingly, although the rats treated with aminoguanidine had less damage in the retina and the optic nerve, their intraocular pressure was no different than in animals that did not receive the drug. This indicates that aminoguanidine did not lower the elevated pressure in these animals. That is important because it means that lowering the pressure is not what protected the retinal ganglion cells.
This encouraging finding gives researchers hope that it may be possible to treat patients whose glaucoma does not respond to pressure-lowering drugs or surgery, as well as a subset of patients who have glaucoma, but no elevation of IOP. Drugs that inhibit NOS-2 might preserve vision in those patients who don’t respond to current therapies and also could be used along with drugs that lower intraocular pressure.
“”The emerging concept of using drugs to protect nerve cells is being aggressively pursued across the country,”” said Carl Kupfer, M.D., director of the National Eye Institute, part of the National Institutes of Health, the federal agency that helped fund the study. “”New approaches to treating glaucoma are welcome, and this work will be followed closely by other glaucoma researchers.””
The significance of these findings may extend beyond glaucoma. Researchers believe that similar processes may be involved in a number of neurodegenerative and neurovascular diseases, including Parkinson’s disease, Alzheimer’s disease and multiple sclerosis.
The research appears in the Aug. 17 1999 issue of the Proceedings of the National Academy of Sciences.
ABSTRACT
Proc Natl Acad Sci U S A 1999 Aug 17;96(17):9944-9948
Inhibition of nitric-oxide synthase 2 by aminoguanidine provides neuroprotection of retinal ganglion cells in a rat model of chronic glaucoma.
Neufeld AH, Sawada A, Becker B.
Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110, USA. neufelda@am.seer.wustl.edu
Glaucoma is an optic neuropathy with cupping of the optic disk, degeneration of retinal ganglion cells, and characteristic visual field loss. Because elevated intraocular pressure (IOP) is a major risk factor for progression of glaucoma, treatment has been based on lowering IOP. We previously demonstrated inducible nitric-oxide synthase (NOS-2) in the optic nerve heads from human glaucomatous eyes and from rat eyes with chronic, moderately elevated IOP. Using this rat model of unilateral glaucoma, we treated a group of animals for 6 months with aminoguanidine, a relatively specific inhibitor of NOS-2, and compared them with an untreated group. At 6 months, untreated animals had pallor and cupping of the optic disks in the eyes with elevated IOP. Eyes of aminoguanidine-treated animals with similar elevations of IOP appeared normal. We quantitated retinal ganglion cell loss by retrograde labeling with Fluoro-Gold. When compared with their contralateral control eyes with normal IOP, eyes with elevated IOP in the untreated group lost 36% of their retinal ganglion cells; the eyes with similarly elevated IOP in the aminoguanidine-treated group lost less than 10% of their retinal ganglion cells. Pharmacological neuroprotection by inhibition of NOS-2 may prove useful for the treatment of patients with glaucoma.
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