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Researchers develop mouse model for studying blinding diseases in humans


Genetically engineered mice closely mimic what happens to people who have dry form of age-related macular degeneration

Researchers at the University of Utah have developed genetically engineered mice that closely mimic what happens to humans who suffer from the juvenile, or dry, form of age-related macular degeneration. The findings are reported in the March 4, 2005 Early Online Edition of the Proceedings of the National Academy of Sciences. The mice express a mutant ELOV4 gene that causes humans to develop from the juvenile form of macular degeneration known as Stargardt disease. The gene was discovered by the same team of University of Utah scientists in 2001. The mutation prevents retinal pigment epithelium cells (RPE) from disposing of cellular waste know as lipofuscin (including the fluorophore A2E).

This buildup of waste causes degeneration of the RPE cells in the central retina and results in progressive vision loss in both humans and mice with the mutation. "To date, these mice provide one of the best models to study both Stargardt disease and a dry form of age-related macular degeneration. Using these mice, it is now possible to test a variety of treatment strategies including cell transplantation, gene therapy and pharmaceuticals," said Kang Zhang, M.D., Ph.D., assistant professor of ophthalmology and visual sciences at University of Utah’s John A. Moran Eye Center and an investigator in the Program in Human Molecular Biology and Genetics at the University’s Eccles Institute of Human Genetics.

Zhang predicts human clinical trials for treatments of the disease could be available in the next three to four years. "By engineering how much of the gene mutation is expressed in the eyes of a mouse, we can create many different ways of the disease presentation and therefore many points to intervene in the disease process," he said.

Patients with Stargardt disease typically begin showing symptoms of vision loss between the ages of 10 and 20. While Zhang doesn’t expect new treatments to restore vision that has already been lost, he says it may be possible to stop further vision loss. Ultimately, he hopes to prevent vision loss before it occurs.

Age-related macular degeneration is the leading cause of blindness in Americans age 50 and older. There is currently no cure for the disease.

In addition to Zhang, the study included researchers from the University of Utah’s Department of Neurobiology and Anatomy, the University of California at San Diego, the Retina Foundation of the Southwest in Dallas, and Brigham Young University.

Kang Zhang, M.D., Ph.D | EurekAlert!
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