Researching the Cause of Macular Degeneration

The causes of age-related macular degeneration (AMD) are still not understood, but researchers at the Medical College of Wisconsin continue to seek answers through research at the cellular level.

Age-related macular degeneration is the leading cause of vision loss for individuals over age 60, affecting 13 million Americans. Macular degeneration affects light-sensitive photoreceptor cells in the macula, the center of the retina at the back of the eye. While it doesn't cause total blindness, the disease destroys central vision so reading, watching TV and driving are impossible. There is no cure, and treatments are very limited.

Like most age-related diseases, AMD is likely to have many causes, including both genetic and "toll of years" components. A gene or several genes may predispose the retina to cellular changes resulting in macular degeneration. But whether or not a person with a genetic predisposition gets the disease also depends upon how the aging process itself affects cells.

A goal of much research on age-related diseases, including macular degeneration, is to understand how cells age so that disease onset can be delayed. If onset can be slowed for many years, individuals with a genetic predisposition for AMD will never suffer symptoms. But it is difficult to study how cells age in a long-lived species such as man. You can't take samples of people's retinas at different stages of life. And a single researcher can't study a disease that takes 60 or more years to develop.

To get around this problem, our team uses a laboratory strategy to study aging cells. We examine a type of cell that supports retinal photoreceptors, called the retinal pigment epithelium or RPE. In AMD, aging RPE cells appear to lose function and die first, then photoreceptor cells degenerate from lack of support. To study what happens to RPE cells as they age, we take RPE cells from eye donors and put them in culture where we force them to age over weeks rather than years. In this way we can sample the cells throughout their life span to investigate the effects of aging.

We are particularly interested in how aging affects RPE cell shape. The tops of RPE cells are in contact with retinal photoreceptors. It is critical that the top of RPE cells have a particular shape and particular molecular composition to support photoreceptors. But as we age, we lose RPE cells, and the remaining cells lose their normal shape. We hope to discover how this occurs so that treatments can be developed to slow age-related changes in RPE cells. In turn, photoreceptor degeneration would also be slowed and vision may be maintained for many more years.

Research into the causes of AMD has helped develop the only treatment options for the disease, including the use of lasers to destroy abnormal blood vessel growth in the so-called "wet" form of age-related macular degeneration. However, for the majority of AMD sufferers, there is no treatment. Our "toll of years" research is an important part of finding a cause, a treatment and a cure for AMD.

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