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Why You Need to Know About Apoptosis

BY WILLIAM D. TOWNSEND, OD
FEBRUARY 1999

You may not have heard about apoptosis, which is programmed cell death or suicide, but it's likely to soon become very important in your understanding of many ocular and systemic diseases.

What Apoptosis Does for You

Apoptosis is responsible for proper embryologic development. It allows us to lose the skin webbing between our digits, and it enables frogs to lose their tails as they grow out of the tadpole stage. Probably over 50 percent of our embryonic neurons die a carefully planned death as a result of an inadequate local supply of Nerve Growth Factor (NGF). Apoptosis is used by the cell to prevent uncontrolled division.

Apoptosis may be at least partially responsible for several degenerative conditions, including AIDS, Alzheimer's disease, parkinsonism and amyotrophic lateral sclerosis (Lou Gehrig's disease). It is also believed to contribute to tissue damage accompanying stroke, heart attacks and alcoholic liver damage. Apoptosis is important in discouraging cancer cell formation, and it may play a vital role in the immunologic system. Cells infected by a virus can sometimes kill themselves before the virus has time to replicate and spread to other cells. Cells die either because they are harmful or because it is more efficient to kill them than to maintain them.

Glaucoma Link

Robert Nickells, Ph.D., and his associates have studied apoptosis as it relates to glaucoma and optic nerve damage. They crushed the optic nerve of rats and studied the concentration of various proteins associated with three genes: the bax gene, which has been shown to stimulate apoptosis; bcl-2, which appears to prevent cell suicide; and gene p53, a tumor suppressor gene which regulates the equilibrium between bcl-2 and bax. They found that in cells dying from apoptosis, bax messenger RNA (which carries the DNA code) is found in greater concentration than bcl-2 messenger RNA. They also found that the presence of p53 was very important in determining whether or not crushed cells were resistant to apoptosis. The group pointed out that the first stage in glaucoma is elevated pressure. Crushing the rat nerve disrupts axoplasmic transport of neurotrophins (neural peptides that activate cellular processes) and eventually induces cell death. Elevated pressure is thought to have the same effect. In the second stage of glaucoma, there seems to be a decrease in the flow of neurotrophins to cells as well as a release of excitatory amino acids, or "excitotoxins," such as glutamate. High concentrations of glutamate have been found in the eyes of glaucoma patients. The increase in excitotoxins and decrease in neurotrophins is thought to induce apoptosis.

At present, our only means of treating glaucoma is lowering intraocular pressure. Medications based on apoptosis research could potentially prevent cell death by altering or blocking expression of the genes that cause the production of cell-killing proteins.

Other Visual Implications

Apoptosis is not limited to nervous tissue. Wilson (1998) has discussed the possibility of apoptosis as a factor in keratocyte changes in keratoconus, and Wilson (1997) and Cavanagh (1998) have also studied apoptosis relative to corneal epithelial sloughing and contact lens wear. Gao, et al. (Cornea, Feb. 1997) found that after photorefractive keratectomy (PRK), rabbit corneas showed a loss of stromal keratocytes beneath the ablation area due to apoptosis, seen up to four weeks after the procedure.

Furthermore, if trauma to the cornea ultimately leads to cell death, we may one day be able to prevent corneal scarring due to injury simply by modifying or blocking apoptosis. CLS

Dr. Townsend is in private practice in Canyon, Texas, and is a consultant at the Amarillo VA Medical Center. (doctorbill@amaonline.com)