UCSD-Utah team develops mouse model to test therapies for macular degeneration

March 04, 2005

Researchers at the University of California, San Diego (UCSD) School of Medicine and the University of Utah have developed a mouse model of Age-Related Macular Degeneration (AMD), the leading cause of blindness in people over age 55, and Stargardt Macular Degeneration (STGD), a form of the disease that affects children and young adults.

The mouse model*, which was reported in the March 4, 2005 online edition of the Proceedings of the National Academy of Sciences, "now permits the testing of potential therapies for the "dry" version of age-related AMD and STGD in an animal model," said the study's co-senior author David S. Williams, Ph.D., UCSD professor of pharmacology and neurosciences. Currently there is no known treatment or cure for the disorder.

AMD affects about 11 million Americans, with dry AMD accounting for about 90 percent of all AMD. STGD strikes about 30,000 children and young adults in the U.S. Macular degeneration is caused by the deterioration of the central portion of the retina, the inside back layer of the eye that records images and sends them via the optic nerve from the eye to the brain. The retina's central portion, known as the macula, is responsible for focusing central vision in the eye, and it controls the ability to read, drive a car, recognize faces or colors, and see objects in fine detail.

The UCSD-Utah scientists said that the AMD and STGD forms of macular degeneration are characterized by high levels of debris called lipofuscin that accumulates in the retinal pigment epithelium (RPE) and results in its degeneration together with photoreceptor cells. Vision loss follows.

Noting that scientists have recently linked mutations in a gene called ELOVL4 to AMD and STGD, the UCSD-Utah investigators developed mice with a mutant form of ELOVL4, which caused the mice to develop significant lipofuscin accumulation and photoreceptor and RPE death in a pattern closely resembling the human counterpart.
-end-
Co-senior author of the study was Kang Zhang, Department of Ophthalmology and Visual Science, Program in Human Molecular Biology and Genetics, Eccles Institute of Human Genetics and Department of Neurobiology and Anatomy, University of Utah, Salt Lake City, Utah. Co-first authors of the paper were G. Karan, University of Utah, and C. Lillo, UCSD Departments of Pharmacology and Neurosciences. Additional authors were D. J. Cameron, Yu Zhao, and C. Li, University of Utah; H. R. Vollmer-Snarr, UCSD; and K.G. Locke, and D.G. Birch, Brigham Young University, Provo, Utah.

The study was supported by the National Institutes of Health and by the Ruth and Milton Steinbach Fund, Ronald McDonald House Charities, the Macular Vision Research Foundation, the Research to Prevent Blindness, Inc., Grant Ritter Fund, American Health Assistance Foundation, the Karl Kirchgessner Foundation, Val and Edith Green Foundation, and the Simmons Foundation.

* There have been other reports of mouse models of AMD, but these models have not replicated the symptoms of dry AMD. Dry AMD accounts of 90 percent of all AMD, while "wet" AMD is relatively minor and involves neovascularization of the back of the retina. A Kentucky group developed a model called Cc1-2 which comes close to modeling wet AMD. Another model is a transgenic mouse that expresses a mutant form of the lysosomal enzyme cathepsin D. While this model showed localized atrophy of the retina, it was the periphery of the retina that was most affected. The only other model is a knockout mouse for the Abca4 gene. Mutations in the equivalent gene in humans result in a recessive form of STGD. However, this mouse does not undergo retinal degeneration.

University of California - San Diego

Related Macular Degeneration Articles from Brightsurf:

Levodopa may improve vision in patients with macular degeneration
Investigators have determined that treating patients with an advanced form of age-related macular degeneration (AMD) with levodopa, a safe and readily available drug commonly used to treat Parkinson's disease, stabilized and improved their vision.

Combating drug resistance in age-related macular degeneration
An international team of researchers led by Baylor College of Medicine and Houston Methodist has discovered a strategy that can potentially address a major challenge to the current treatment for age-related macular degeneration,

Study finds unexpected suspect in age-related macular degeneration
Scientists have identified an unexpected player in the immune reaction gone awry that causes vision loss in patients with age-related macular degeneration (AMD), according to a new study published today in eLife.

Potential way to halt blinding macular degeneration identified
It would be the first treatment for dry age-related macular degeneration and could significantly improve treatment for wet AMD.

Heating techniques could improve treatment of macular degeneration
Age-related macular degeneration is the primary cause of central vision loss and results in the center of the visual field being blurred or fully blacked out.

Eye's vulnerability to macular degeneration revealed
Scientists have found significant differences in the shape and biology of the same type of cell taken from different parts of the retina, according to a study in eLife.

Hallucinations associated with brain hyperactivity in people with macular degeneration
New research from The University of Queensland has shown for the first time that visual hallucinations in people with macular degeneration are associated with abnormally heightened activity in the visual cortex of the brain.

Eating leafy greens could help prevent macular degeneration
A new study has shown that eating vegetable nitrates, found mainly in green leafy vegetables and beetroot, could help reduce your risk of developing early-stage age-related macular degeneration (AMD).

An orange a day keeps macular degeneration away: 15-year study
A new study has shown that people who regularly eat oranges are less likely to develop macular degeneration than people who do not eat oranges.

Macular degeneration linked to aging immune cells
Studying mice and cells from patients, vision researchers at Washington University School of Medicine in St.

Read More: Macular Degeneration News and Macular Degeneration Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.