Two genetic studies involving thousands of participants suggest that age-related macular degeneration, an eye disease common among the elderly, is tied to a gene that helps regulate “good” cholesterol. The studies present the first genetic evidence of a link between cholesterol and the disease, and they may lead scientists to identify new targets for therapy.
Age-related macular degeneration is the leading cause of blindness in older adults in the United States. Lesions form behind the retina, impeding the center of an individual’s field of vision. A link between cholesterol and an eye disease might sound strange, but scientists have known for years that cholesterol can accumulate at the back of the eye as part of aging. Moreover, cholesterol is a major component of the macular lesions. What role cholesterol plays in the eye, however, remains unclear.
In the new work, scientists compared the genomes of people who have macular degeneration with the genomes of healthy individuals to search for genetic variants that occur more frequently among one group or the other.
In the first study, Johanna Seddon, a genetic epidemiologist at Tufts University in Boston and colleagues scanned the genomes of 979 people with advanced degeneration and 1709 healthy people. The researchers found a strong association with a variant of the hepatic lipase gene (LIPC). LIPC codes for an enzyme involved in the metabolism of HDL, or “good,” cholesterol. People with this variant had an 18% reduced risk of having the disease. A scan of 4337 other cases and 2077 controls yielded the same result. The researchers also found weaker associations with three other genes involved in the HDL pathway: ABCA1, CETP, and LPL. These weaker associations did not meet the strict criteria necessary in this type of study to achieve statistical significance.
In the second study, a team led by Anand Swaroop, a molecular geneticist at the National Eye Institute in Bethesda, Maryland, confirmed the same link between macular degeneration and LIPC. The researchers also independently connected the disease to ABCA1, CETP, and LPL when they scanned the genomes of 2157 people with macular degeneration and 1150 controls. Both studies appear online today in the Proceedings of the National Academy of Sciences.
These results point to a relationship between the HDL pathway and risk of age-related macular degeneration, but they don’t explain that connection. One idea, Seddon says, is that HDL may act as a transport system for the eye, ferrying in nutrients that protect the retina from the bloodstream.
It’s a plausible mechanism, says Christine Curcio, a histopathologist at the University of Alabama, Birmingham, who was not involved with the work. “If there's some variant that causes [that nutrition system] to be less efficient,” she says, “that could have some long-term effect on susceptibility to eye disease.”
Curcio anticipates that these papers will prompt more research aimed at understanding the role of cholesterol in the eye, which could help scientists identify potential drug targets. Pharmaceutical companies may not necessarily have to develop new medications, however. Curcio says existing cholesterol drugs delivered locally to the eye may benefit patients. “We can piggyback on decades of hard work in service of understanding heart disease,” she says.
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