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UCSD-Utah Team Develops Mouse Model To Test Therapies For Macular Degeneration

Date:
March 20, 2005
Source:
University Of California - San Diego
Summary:
Researchers at the 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.

Researchers at the 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.

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.


Story Source:

The above story is based on materials provided by University Of California - San Diego. Note: Materials may be edited for content and length.


Cite This Page:

University Of California - San Diego. "UCSD-Utah Team Develops Mouse Model To Test Therapies For Macular Degeneration." ScienceDaily. ScienceDaily, 20 March 2005. <www.sciencedaily.com/releases/2005/03/050309103248.htm>.
University Of California - San Diego. (2005, March 20). UCSD-Utah Team Develops Mouse Model To Test Therapies For Macular Degeneration. ScienceDaily. Retrieved October 21, 2014 from www.sciencedaily.com/releases/2005/03/050309103248.htm
University Of California - San Diego. "UCSD-Utah Team Develops Mouse Model To Test Therapies For Macular Degeneration." ScienceDaily. www.sciencedaily.com/releases/2005/03/050309103248.htm (accessed October 21, 2014).

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