Mouse Model Developed for AMD and Stargardt's Research

by Dan Roberts
March 2005
A research team 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) and Stargardt’s disease. As reported in the online edition of the Proceedings of the National Academy of Sciences (March 4, 2005), the mouse model is the first to replicate the symptoms of the most common form (dry) of age-related macular degeneration and of Stargardt’s disease, a juvenile form of the disease. Another mouse model has been developed for Stargardt’s to study a mutated form of the ABCR4 gene, but that model does not display retinal degeneration.
This mouse model displays significant accumulation of lipofuscin (debris accumulated in the retinal pigment epithelium, or RPE) as a result of a mutation in the gene called ELOVL4, which has been found to be common to both conditions in humans. Accumulation of lipofuscins in the retina inhibits nourishment of the photoreceptor cells by the RPE, resulting in degeneration and vision loss. The development of a mouse model will allow researchers to now test potential therapies for both dry ARMD and Stargardt’s disease in an animal–a practice that has not been possible in the past.
Co-senior authors of the study were David S. Williams, Ph.D. (UCSD professor of pharmacology and neurosciences) and 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).

Accutane May Inhibit Progression of Stargardt's Disease

by Dan Roberts
April 2003
Accutane, a prescription drug used to treat acne, has been shown to inhibit the development of lipofuscin deposits in the retinas of rodent models. This is promising news for people with Stargardt’s disease.
The author of the study is Dr. Gabriel Travis, professor of ophthalmology and biological chemistry at the David Geffen School of Medicine at the University of California, Los Angeles. In an article published in Proceedings of the National Academy of Sciences, Dr. Gabriel reported that accutane successfully supressed the buildup of lipofuscin, toxic pigments which lead to loss of central vision.
Dr.Travis stressed that the drug will not cure Stargardt’s disease, and that clinical trials need to be started to test his findings. Stargardt’s disease is caused by a defect in the ABCR gene, disrupting a protein which normally flushes out all-trans-retinaldehyde from the photoreceptor cells. When this byproduct is not removed, lipofuscin collects. Accutane seems to inhibit the formation of all-trans-retinaldehyde, which keeps the genetic defect from destroying vision.
Accutane has been linked to serious side effects, including depression and suicide. It is important to remember that the drug is still undergoing testing as a treatment for Stargardt’s disease, and that patients should not try using it on their own for this purpose.