June 28, 2002 ANN ARBOR — University of Michigan Kellogg Eye Center researchers have found that the aging of the human retina is accompanied by distinct changes in gene expression.
Using commercially available DNA slides, a team of researchers directed by Anand Swaroop, Ph.D., have established the first-ever gene profile of the aging human retina, an important step in understanding the mechanisms of aging and its impact on vision disorders.
In the August issue of Investigative Ophthalmology and Visual Science, Swaroop and colleagues show that retinal aging is associated, in particular, with expression changes of genes involved in stress response and energy metabolism.
The term gene expression means that in any given cell, only a portion of the genes are expressed or switched on. For example, a person's pancreas and retina have the same genes, but only the pancreas can turn on the genes that allow it to make insulin.
Swaroop believes that the findings will help scientists understand whether age predisposes one to changes in the retina that, in turn, lead to age-related diseases. For vision researchers, one of the most pressing disorders is age-related macular degeneration (AMD), a progressive eye disease that affects the retina and results in the loss of one's fine central vision.
"While we still don't know what causes AMD, we do know that the strongest factors are age and family history," says. Swaroop. "We are likely to find that AMD is caused by a complex interaction between genetic and environmental risk factors."
Microarray technology is an important tool for gene profiling because it allows rapid comparison of thousands of genes, something that was unheard of even few years ago. Shigeo Yoshida, M.D., Ph.D., a post-doctoral research fellow in Swaroop's laboratory, examined microarray slides containing DNA from 2,400 human genes.
After identifying the genes expressed in the retina (about half, or 1,200 genes), the researchers compared the expression of these retinal genes in young and old individuals and concluded that expression of 24 genes were altered during aging.
Swaroop wonders whether some people carry genetic variations or weaknesses that are expressed clinically later in life. For such persons, the aging process may trigger or reveal the variation, which may then lead to AMD. By contrast, a person who does not carry the variation may undergo a similar degree of genetic or cellular deterioration from aging, without triggering the disease.
A logical next step for the Kellogg researchers is to study a wider array of genes, which Swaroop hopes will lead to a broader understanding of the molecular events that modulate aging of the retina. Under Swaroop's direction, the U-M Kellogg Eye Center has established a Gene Microarray Facility, which is now generating microarrays of thousands of eye genes.
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