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Genetic links could unlock clues to leading cause of blindness

26.07.2005


Researchers pinpoint chromosome region and genetic markers for macular degeneration in humans, rhesus monkeys



Age-related macular degeneration is the leading cause of blindness in older adults, yet researchers are still in the dark about many of the factors that cause this incurable disease.

But new insight from University of Florida and German researchers bout a genetic link between rhesus monkeys with macular degeneration and humans could unlock secrets about the earliest stages of the disease, when severe vision loss could still be stopped.


The researchers pinpointed a chromosome region and genetic markers for macular degeneration in humans and rhesus monkeys, findings recently published in the online edition of the journal Experimental Eye Research. Linking the disease in monkeys to the disease in humans allows researchers to study how it progresses in the animals, which could lead to better treatments and even a cure.

"Stopping the development of the disease is something the monkeys will help us do that we can’t do with humans," said William W. Dawson, a UF professor of ophthalmology and physiology and a co-author of the study. "This is a big step forward in dealing with the disease."

The researchers studied seven genetic sites in the monkeys that correspond to human chromosomes linked to macular disease. One of those areas, the findings confirm, contains genes that predict age-related macular degeneration in humans and rhesus monkeys. Dawson and other researchers have suspected for years that the disease was very similar in humans and monkeys, but these findings finally establish that. This discovery, he said, will allow researchers to delve deeper into what causes the disease and could be the first step toward repairing the genetic defects linked to it.

According to the National Eye Institute, nearly 2 million Americans have advanced age-related macular degeneration, a disease that develops when a small, light-detecting part of the retina called the macula breaks down. Seven million more Americans have an intermediate form of the disease, and millions more are expected to develop it within the next 15 years.

The disease causes nodule-like specks to build up in the eye, chipping away central vision over time. But Dawson said most people don’t even realize something is wrong until they detect changes in their vision. The disease can be controlled, but there is no known way to reverse the vision loss it causes.

Knowing more about the earliest predictors of macular degeneration could help doctors treat the disease before extensive vision loss occurs and may even prevent it in some people. The early risks associated with macular degeneration have been difficult for researchers to study in humans, and as a result, doctors know little about this aspect of the disease, Dawson said.

"It’s difficult to follow closely the aging of a human over a specific period of time," he said. "People wouldn’t tolerate a controlled (living) environment for weeks and years."

One of the biggest problems researchers have faced is determining how much of a role genetics plays versus lifestyle and environmental factors such as blue light, part of the spectrum of natural visible light. Frequent exposure to blue light rays has been linked to macular degeneration. If the disease is going to be treated early, Dawson said researchers must know the significance of these factors.

Aside from studying early environmental risks, the next step for researchers is to map the specific genes at work, said Dawson, who worked on the study with German geneticist Jorg Schmidtke. But because more than one gene is likely involved, this task will not be easy, Dawson said.

Dr. Johanna M. Seddon, a Harvard Medical School associate professor and director of the epidemiology unit of the Massachusetts Eye and Ear Infirmary, said studies conducted on 840 human twins have shown that genetics plays a significant role but not the only role. Even diet plays a big part, she said. Her own research with the National Eye Institute has shown that taking certain vitamins and minerals can reduce the risk of developing the disease by 25 percent over five years.

"With the increasing number of people living beyond the age of 85, it heightens the importance of this disease and the concern about (what will happen) if we don’t come up with a better way to treat this," she said.

That’s where Dawson thinks the monkeys can help. They age three to four times faster than humans, making it easier to track the progression of the disease. The monkeys also can remain in a controlled environment to test nongenetic factors, and their families can be studied more extensively.

Although most rhesus monkeys never show signs of macular degeneration, between 30 percent and 70 percent of the monkeys Dawson’s team studied do. That’s because these primates are the descendents of 50 monkeys brought to live on a Puerto Rican island just before World War II. The free-ranging monkeys on the island have multiplied to near 1,500, but because the rhesus monkeys are not native to the area, they could mate only with each other. This inbreeding has predisposed the monkeys to various genetic diseases, such as age-related macular degeneration.

Unlike most other animals, a rhesus monkey’s eyes have the same complex structure as a human eye, making them a model study subject. They’re so similar, he said he sometimes slips images of rhesus monkey eyes into presentations for medical residents to see if anyone notices the difference.

"I haven’t been caught yet," he said. "Only the most expert would detect the differences."

April Frawley Birdwell | EurekAlert!
Further information:
http://www.health.ufl.edu

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