~Glaucoma, Part 3 - Other Causes and Treatments

OTHER POSSIBLE CAUSES
  • Glutamate's Role in Glaucoma
  • Cell Death Apart from Glutamate
  • Pigment Dispersing Syndrome
Glutamate's Role in Glaucoma

Agreement on the importance of preventing the death of retinal ganglion cells has been established, but the cause of ganglion cell death remains speculative. Present information supports the hypothesis that ganglion cell death may result from a form of ischemia (decreased blood flow to a body organ or part). During ischemia, glutamate is released in excessive amounts, initiating the death of neurons. Glutamate is a salt of glutamic acid, a nonessential amino acid occurring in a wide number of proteins. Glutamate is considered a good guy/bad guy. Because brain cells use glutamate as a neurotransmitter, it may rightly be termed a "great communicator" as signals leap from neuron to neuron. Effective communication also means the controlled release of glutamate, as precise amounts are delivered to the proper cells. It is when glutamate occurs in excessive amounts that trouble begins. Communication between cells fails, and exorbitant amounts of glutamate attach to cells having glutamate receptors. This bonding or attachment spells doom to the ganglion cell, resulting in eventual cell death. Excesses of glutamate have, in effect, poisoned the cell.

Elevated glutamate levels can also exist in the vitreous humor of patients with glaucoma (27 mM as compared to 11 mM in controls) (Vorwerk et al. 1999a). The vitreous humor fills the posterior compartment of the eye, assisting in holding the retina and lens in place. An increased concentration of glutamate in the vitreous humor is sufficient to induce retinal ganglion cell death (Vorwerk et al. 1999b). The rise in IOP is probably the initial insult, which enhances the increase or release of glutamate. Supplements that protect against glutamate toxicity will be discussed later in this protocol.

Cell Death Apart from Glutamate

Two other major causes of cell death are the influx of calcium into the cell and the generation of free radicals. Substances that prevent activation of the glutamate receptor, calcium entry, or free-radical damage may be regarded as neuroprotective agents. Recall that magnesium, in assessing nutritional pharmacology, is considered a calcium channel blocker. Broad-spectrum antioxidants have long been known to quench the harmful activity of free radicals. Ideally, for a substance to have a role as a neuroprotective agent in glaucoma, it should be delivered topically to the eye and used repeatedly.

Pigment Dispersing Syndrome

Another cause of glaucoma is considered to be the pigment dispersing syndrome (PDS) or pigmentary glaucoma. In PDS, the concavity (curving inward) of the mid-peripheral iris allows iridozonular contact, causing a shedding of the pigmented iris. Released pigment is then carried to the trabecular meshwork where it can reside benignly, not affecting the IOP, or it can malignantly elevate the IOP, as in pigmentary glaucoma. Flattening of the concave iris by mitotic therapy and laser iridotomy appears the key to current and future management. Studies confirm that PDS is inherited as an autosomal dominant trait, observed most frequently in young, myopic (nearsighted) men (Campbell et al. 1995). An autosomal dominant trait is one in which the inheritance of a dominant gene on an autosome, not a sex chromosome, causes the characteristic to be expressed.

Note: Primary juvenile glaucoma is a rare form of glaucoma that typically affects individuals from 3-20 years of age, and it, too, is an autosomal dominant trait (Wiggs et al. 1995).

In some individuals, exercise causes pigment release and an increase in IOP, contributing to the complexities of PDS management. A study conducted at the Institute of Ophthalmology in Italy determined that exercise-induced pigment release temporarily obstructs the aqueous outflow channels, causing IOP increase in some patients with PDS. Pre-exercise treatment with dapiprazole, an alpha-adrenergic blocking agent, was useful in reducing IOP spikes and increasing outflow facilities after intensive exercise (Mastropasqua et al. 1995; Mastropasqua et al. 1996).

Scientists are one step closer to locating the gene responsible for PDS. The New England Medical Center in 1997 stated that the telomeric end of the long arm of chromosome 7 appears incriminated in PDS. Locating a gene responsible for this condition is the first step toward the isolation of the gene itself. Characterization of the responsible gene will potentially lead to new methods of diagnosis and treatment. PDS is one type of glaucoma, accounting for 12-15% of all cases of blindness each year.

TREATMENT OPTIONS
  • Current Drug Therapy
  • Supplements
  • Diet
  • Eye Drops
  • Lifestyle Changes
Current Drug Therapy

Betaxolol, a beta-blocker presently used to reduce IOP, has calcium channel-blocking functions. Experimental studies show that betaxolol is an efficient neuroprotective agent against retinal ischemia in animals when injected directly into the eye or intraperitoneally. Betaxolol exerts its primary neuronal actions on retinal ganglion cells. Unfortunately, betaxolol has an aggressive list of side effects.

Interviews with hospital pharmacists revealed two prescription drugs being filled with more regularity than others for the treatment of glaucoma. Timoptic eye drops, a beta-adrenergic blocking agent, represents an older, but still popular, approach to treating glaucoma. Xalatan, a prostaglandin analogue, generically known as latanoprost, is a newer method of treatment. Its mechanism of efficacy deals with replicating the activity of prostaglandins, hormone-like unsaturated fatty acids that act in minuscule amounts on local target organs. Latanoprost reduces IOP by increasing the outflow of aqueous humor.

Research conducted at the University of Nebraska Medical Center involved 272 patients taking latanoprost for one year (Camras et al. 1996). Of those enrolled in the study, about 70 individuals withdrew before the end of the study. Withdrawals were caused in 1% by inadequate control of IOP; 5% because of increased iris pigmentation; 3% because of other ocular problems; and 17% because of unrelated medical and nonmedical reasons. The final consensus was that latanoprost safely and effectively reduces IOP for one year, evidencing its usefulness in POAG. However, latanoprost usage can cause a darkening of the pigment in the iris, which might aesthetically disappoint a unilateral glaucoma patient.

Supplements That May Lessen Neurotoxicity and Glaucoma Progression

Experimental studies have identified a variety of naturopathic substances that may prove useful in preventing the death of retinal neurons, particularly ganglion cells, induced by ischemia. It may be possible to protect cells against glutamate toxicity by taking methylcobalamin supplements, the biologically active form of B12 (Akaike et al. 1993; Kikuchi et al. 1997). Methylcobalamin is immediately active upon absorption, although cyanocobalamin must be converted to either methylcobalamin or adenosylcobalamin by the body, removing the cyanide molecule and adding either a methyl or adenosyl group.

Note: The amount of cyanide produced in the conversion process is extremely small.

Acetyl-L-carnitine is said to possess efficacy by attenuating age-related neural deficits. Acetyl-L carnitine has produced stunning results in protecting neurons in a wide range of disease processes.

The antioxidant activities of lacrimal fluid and blood plasma were studied in glaucoma, as compared to normal eyes (Makashova et al. 1999). The findings indicate that the progress of glaucoma is paralleled by a gradual decrease in the lacrimal fluid antioxidant levels. A broad-spectrum antioxidant is a recommendation frequently made by various national and international researchers with regard to glaucoma treatment. The antioxidant complex should provide 200-400 IU of vitamin E daily.

Alpha lipoic acid (ALA), both water- and fat-soluble, is a vitamin-like antioxidant, sometimes referred to as the "universal antioxidant." Dr. Lester Packer, a scientist who heads the Membrane Bioenergetics Group at the University of California, regards lipoic acid as a "free agent," meaning that it can substitute for the other antioxidants when they are in short supply. Primary evidence indicates that 150 mg of alpha lipoic acid, taken daily for 1 month, improves visual function and ocular hypertension in glaucoma patients (Filina et al. 1995).

Thiamine (vitamin B1) has been used to improve visual acuity (van Noort et al. 1987). This may be of particular advantage to glaucoma patients, for thiamine-deficient states are frequently associated with glaucoma (Asregadoo 1979).

Can Diet Make a Difference?

The watchful selection of foodstuffs appears to be another modality that impacts the control level of glaucoma. The value of vitamin C has been documented with regard to both lowering IOP and maintaining the reliability of ocular collagen (Pfister 1980; Pasquali et al. 1997; Head 2001). For this reason, glaucoma patients should acquaint themselves with foods rich in this essential vitamin and use them freely in meal planning.

Fresh fruits and vegetables are reliable sources of vitamin C. Select from kiwi, bell peppers, broccoli, cabbage, citrus fruits, Brussels sprouts, kale, parsley, strawberries, tomatoes, and cantaloupe to contribute to an adequate vitamin C intake. Remember to emphasize dark-colored berries (raspberries, blackberries, blueberries), grapes, raisins, and plums, which are sources of anthocyanoside antioxidants having a special affinity for the eye.

Try to plan a diet around whole, unprocessed foods, including whole grains, legumes, nuts, and seeds.

The omega-3 fatty acids have shown benefit in lowering IOP (Kulkarni et al. 1989). One tbsp of flaxseed oil (a source of alpha-linolenic acid) daily provides a good supply of omega-3 fatty acids. Because flaxseed oil is highly polyunsaturated, it should not be heated.

Evidence is mounting pertaining to excitatory neurotoxins encountered in our food supply. The most frequently encountered food excitotoxin is glutamate, which is commercially added to many foods despite evidence that it can freely penetrate certain brain regions and rapidly destroy neurons by hyperactivating glutamate receptors (Olney 1994). Avoidance of glutamate may be of particular advantage to individuals with glaucoma.

The herb oregano, from the mint family, may have a worthwhile place in the diet of a glaucoma patient. James A. Duke, Ph.D. (1997) suggests that of the 60 mints he investigated, all high in antioxidant value, oregano had the highest concentration of antioxidants. He suggests using 1-2 tsp of dried oregano per cup of boiling water. The therapeutic strength of this drink can be amplified with the addition of peppermint and rosemary.

Identify and eliminate the consumption of allergenic substances in ingested food materials. Allergies are individualized and impossible to distinguish universally, but milk, onion, eggs, and chocolate are among the most common in patients.

Drink at least 48 oz of clean water daily. This amount should be metered throughout the day, with at least 1-hour intervals, consuming only a few ounces at one time. Individuals who enjoy juice in their diets or support the healing benefits associated with juice may wish to combine bilberry, cranberry, and huckleberry, all of which are high in anthocyanosides. Avoid stimulating beverages, such as coffee and tea, which cause vasoconstriction and elevated blood pressure.

Topical Eye Drops

Research shows that orally taken antioxidants will effectively raise blood plasma levels of the nutrients, but the intake does not always correlate directly in eye tissues. In one study, oral antioxidant therapy normalized blood antioxidant levels in advanced glaucoma patients but did not help lacrimal antioxidant activity. Although further research needs to be conducted, this may indicate that topically applied antioxidant eye drops may be the preferred treatment in glaucoma patients (Makashova et al. 1999).

Lifestyle Changes

Glaucoma is considered to be a stress disease. Avoid emotional upsets and upheavals, for external pressure increases internal ocular pressure (Kaluza et al. 1996; Flammer et al. 1999). Try to develop a composed, peaceful lifestyle. Climates with great temperature variances are thought to be detrimental. More stable climates and temperatures appear to be better tolerated by the glaucoma patient. Don't smoke, for tobacco constricts blood vessels, reducing the blood supply to the eye. Avoid prolonged eye stresses such as long movies, excessive TV viewing, or excessive reading.

Discuss with your ophthalmologist your physical and sexual activity. Normally, after treatment, regular exercise and activities are resumed. Restraint should be observed to avoid fatigue. Sexual relations are usually permitted, when eye pressure is under control.

Continued . . .


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