Apolipoprotein E (apoE) is a protein component that helps transport cholesterol in the blood between the liver and other tissues, says Steven Fliesler, Ph.D., professor and director of research in the department of ophthalmology at Saint Louis University School of Medicine and lead investigator. It also is present in the brain and other nervous tissues, including the retina.
There are three genetically determined forms of apoE (apoE-2, apoE-3 and apoE-4), each encoded by a specific sequence of DNA . Studies suggest that apoE-3 may play a protective role in the nervous system, assisting in the repair of nervous tissue, such as after a brain injury.
On the other hand, people who have elevated levels of the apoE-4 version of the protein are at an increased risk for developing the late onset, familial type of Alzheimer’s disease.
The mystery SLU researchers are now trying to solve is why the reverse seems to be true when it comes to advanced macular degeneration.
“Paradoxically, the exact opposite trend seems to prevail,” Fliesler says. “ApoE-4 seems to correlate with a reduced incidence of macular degeneration.”
For the next two years, Fliesler and his team will test whether the presence of one or the other form of apoE slows down, quickens, or does essentially nothing to the rate of retinal degeneration in genetically altered mice that undergo progressive, age-dependent vision loss. Fliesler’s team will selectively introduce either the human apoE-3 or apoE-4 gene into the mice and then study what effects this may have on the structure and function of their retinas.
“We hope our experiments with transgenic mice will provide some clues as to what apoE is doing in the retina and why one form of apoE versus another would predispose someone to having macular degeneration,” Fliesler says. “At this point, it makes no sense to me that the same molecule would have very different actions in the brain versus the retina, both of which are nervous tissue,” he says.
Macular degeneration, which affects nearly 12 million people in the United States - about one in four older adults – and about 50 million worldwide, is caused by the deterioration of the central portion of the retina, known as the macula. 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.
As people age, their chances for developing eye diseases increase dramatically. Smoking is also a strong risk factor, as it seems to be for other age-related diseases.
As the baby boomers get older and the average human lifespan continues to increase, these diseases will have an increasingly significant impact on society, including quality of life for the elderly as well as worldwide escalating healthcare costs, says Fliesler.
Established in 1836, Saint Louis University School of Medicine has the distinction of awarding the first M.D. degree west of the Mississippi River. Saint Louis University School of Medicine is a pioneer in geriatric medicine, organ transplantation, chronic disease prevention, cardiovascular disease, neurosciences and vaccine research, among others. The School of Medicine trains physicians and biomedical scientists, conducts medical research, and provides health services on a local, national and international level.
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