Sarah Goodwin

Kathi Ovnic
Holly Korschun
October 4, 1999



A dietary compound found in fruits may help prevent the development of age-related macular degeneration (ARMD), the leading cause of legal blindness in the United States, according to a recent study by scientists at Emory University. The research was published in the August 1999 issue of Investigative Ophthalmology and Visual Science.

Paul Sternberg, Jr., M.D., Emory professor of ophthalmology and Dean P. Jones, Ph.D., Emory professor of biochemistry, found that the compound dimethylfumarate (DMF), induces the synthesis of glutathione (GSH), which has been shown in previous studies to prevent oxidative damage to cells by detoxifying harmful compounds.

The Emory scientists treated human retinal pigment epithelial (hRPE) cells in culture with increasing concentrations of DMF, then analyzed GSH concentrations after 24 hours. They found that as they increased DMF concentrations gradually to a level of 200µM, GSH concentrations increased to two and a half times the level found in the control culture. At levels higher than 200µM, DMF concentrations proved toxic to the cultured hRPE cells. During the first three hours of the experiment, the DMF caused a decrease in GSH concentration, followed by a substantial increase by eight hours. Drs. Sternberg and Jones determined that this initial decrease in GSH levels was caused when DMF formed a conjugate with GSH. Although this decrease temporarily made hRPE cells more susceptible to oxidative damage, the subsequent increase in GSH provided greater protection for hRPE cells against oxidative damage.

"Although it has not been conclusively proven that oxidative injury causes ARMD, studies do suggest that ARMD may be linked to oxidative injury of the retinal pigment epithelium (the cells that cover the pigmented part of the retina)," Dr. Sternberg says. "Our previous laboratory studies have shown that enhancing the synthesis of GSH protects hRPE cells from oxidative injury in cultured hRPE cells and that a diet of antioxidant-rich fruits and vegetables is associated with higher levels of GSH." A large-scale study currently is underway to test the effectiveness of antioxidant or zinc supplements in preventing the onset or retarding the progression of ARMD.

The Emory researchers selected DMF as a model compound because DMF has been shown to increase GSH-dependent detoxification systems in animal tissues in the laboratory. DMF also is relatively non-toxic.

"Our research suggests a dietary method of augmenting the antioxidant capability of human retinal epithelial cells without using antioxidant supplements," Dr. Sternberg says. "DMF increases GSH-dependent detoxification enzymes and can enhance cellular defenses against oxidative injury in the retina. Consumption of DMF in the diet in conjunction with vitamins may be the best way to protect against macular degeneration."

"The use of non-nutritive dietary components for prevention of macular degeneration represents a new strategy to combat the disease," Dr. Jones says. "Supply of more antioxidants is already underway, both in terms of dietary recommendations and clinical trials. Our study shows that, in principle, we could improve protection by consumption of foods containing chemicals that induce our cells to produce more of the antioxidant glutathione. This is very similar to the chemoprevention strategy for certain types of cancer. By eating foods that maximize our natural defense systems, we should be able to reduce risk."

The scientists hope further research will show whether the initial decrease in GSH with DMF treatment could pose any health risk, whether the increases seen in GSH can be achieved in vivo as well as in laboratory cultures, and whether these increases can be sustained over long periods of time.

The research was supported by the National Institutes of Health and Research to Prevent Blindness.