Mouse eyes help U. study

Debbie Moss has described her sight as "Swiss cheese" because of the little pinprick holes missing in her central field of vision. It's a problem she shares with three of her four children.

They have Stargardt disease, the juvenile form of macular degeneration, caused by an inheritable gene mutation. She was diagnosed when she was 21 after years of seeking a solution, but her doctors then said there was a 95 percent chance she wouldn't pass it on.

Like many diseases, the medical world is still unlocking secrets of macular degeneration, learning about potential treatments and discovering the mechanisms that drive it. And some of the most important work is being done at the University of Utah.

U. researchers created a mouse model that mimics what happens to human patients who have either the juvenile or the dry form of age-related macular degeneration, said Dr. Kang Zhang, an ophthalmology and genetics researcher at the U. The work involved researchers in the Department of Ophthalmology and Visual Sciences, in the Program in Human Molecular Biology and Genetics at the Eccles Institute of Human Genetics, and in the Department of Neurobiology and Anatomy.

The mouse models they made are considered the best available.

The Proceedings of the National Academy of Sciences on Monday published a paper on the work in its Online Early Edition.

Age-related macular degeneration is the leading cause of blindness in those 50 and older. Stargardt's appears before age 20, first as a loss of central vision. The retina of someone with Stargardt shows a macular lesion surrounded by yellow-white spots with irregular shapes. The macula, located in the center of the retina, is responsible for fine, detailed central vision used in reading and seeing in color. Eyeglasses and contact lenses cannot replace the vision lost, according to the Foundation Fighting Blindness.

Ninety percent of those with age-related macular degeneration have the dry form, caused by hardening of the arteries that feed the retina. It's marked by retinal pigment atrophy and formation of yellowish deposits in the macula. In both diseases, central vision declines.

To create the two mouse models, one for each form of the macular degeneration, the researchers introduced the human gene ELOVL4 — which Zhang's lab in 2001 identified as responsible for both forms — into mouse embryos. As the mice grow up, the same photo receptor degeneration and retinal pigment atrophy occur.

The researchers control the amount of the gene that is expressed in each mouse, which allows them to study it, the impact of potential treatments at various stages and more.