Study of vision disorder leads to discovery of new family of io...( estigators/nathans.html>Jeremy Nathans ...)

Two separate groups of scientists identified the bestrophin protein in 1998, but it was not clear what it might do, according to Nathans. Thats where the field has been stuck.

Nathans and HHMI research associate Hui Sun, who together had previously discovered the function of a protein responsible for a different form of hereditary macular dystrophy, decided to try to decipher the bestrophin mystery.

Each time we study a hereditary macular dystrophy, we are looking at macular degeneration from another starting point in the disease mechanism, said Nathans. By studying hereditary forms of the disease, scientists gain clues that can help them understand the more common age-related disorder, Nathans said. For example, ophthalmologists have noticed that macular degeneration seems to start by accumulation of material in the retinal pigment epithelium (RPE), the exact region where the bestrophin protein is located.

The retina is like a Ferrari, said Nathans. It is a high performance, high maintenance tissue. The RPE is like the liver and kidney of the retina. It helps keep the retina running. Best disease teaches us that defects in the RPE can initiate macular degeneration.

It was useless to try to guess the function of the bestrophin protein based on comparing it to other proteins of known function, said Sun, because it didnt look like any other known protein. This was a bioinformatics nightmare, he said. At the time we started, the future direction was pretty murky. But this puzzle intrigued us. We wondered what was happening here.

By studying what was known about Best disease, the scientists concluded that the bestrophin protein might be an ion channel because patients with the disease have abnormal readings on
'"/>

Contact: Jim Keeley
keeleyj@hhmi.org
301-215-8858
Howard Hughes Medical Institute
16-Apr-2002