Researchers have shown that the genetic variation in the DNA of mitochondria, the cell’s ‘power plant’ contributes to a persons risk of developing macular degeneration. The mitochondria are the principal energy source of the cell, converting nutrients into energy and performing other specialized tasks. These ‘power plant’ cells are found everywhere in the body except for mature red blood vessels. Having research that shows these cells contribute to the risk associated with the eye disease macular degneration may provide insight on how this eye disease develops.
Vanderbilt investigators have shown how a persons risk of developing macular degeneration is increased due to a genetic variation in the DNA of mitochondria – the ‘power plant’ of cells. The study is the first to examine the mitochondrial genome for changes associated with macular degeneration, the leading cause of blindness in caucasians over 50.
Most people dont realize that we have two genomes, said lead author Jeff Canter, M.D., M.P.H., an investigator in the Center for Human Genetics Research. We have the nuclear genome the human genome that makes the cover of all the magazines, and then we also have this tiny genome in mitochondria in every cell.
Canter teamed with Jonathan Haines, Ph.D., and Paul Sternberg, M.D., experts in macular degeneration genetics and treatment, to examine whether a particular variation in the mitochondrial genome is associated with the eye disease. The genetic change occurs in about 10 percent of Caucasians, referred to as mitochondrial haplogroup T.
Suspecting that this gene variant will be one of a small group of important genetic variants that underly macular degeneration, Canter said. By knowing this we have a better chance of predicting accurately who will get the eye disease.
Macular degeneration as many as 10 million people in the United States, robbing them of the sharp central vision necessary for everyday activities like reading, driving, watching television, and identifying faces. The toll of the eye disease is expected to mount as the U.S. population ages.
The genetics of macular degeneration has been a hot area lately, Canter said. Haines led a team that identified a variant in the Complement Factor H (CFH) gene as accounting for up to 43 percent of macular degeneration. Variations in ApoE2 and a gene called LOC387715 on chromosome 10 have also been linked to the eye disease, and Haines and colleagues demonstrated an interaction between the chromosome 10 gene and smoking in raising macular degeneration risk.
The current study also examined variation in these nuclear genes in 280 cases and 280 age-matched controls, and demonstrated that the mitochondrial genome variation was independent of the known nuclear factors.
Were at the stage where we can use genetic information to predict who is likely to develop macular degeneration well before they actually develop it, said Haines, director of the Center for Human Genetics Research. Now we can conduct trials of preventive treatments somethings that never been possible before.
Sternberg, G.W. Hale Professor and Chairman of the Vanderbilt Eye Institute, is leading a trial to test preventive measures in macular degeneration.
Variation in the mitochondrial genome reflects human migrations and different environmental exposures. Changes in the mitochondrial DNA can alter the efficiency of energy generation and lead to over-production of reactive oxygen species free radicals that can damage the cell.
By identifying genetic changes associated with the mitochondria, our results lend additional confirmatory evidence for the role of oxidative stress in macular degeneration, Sternberg said. This supports study of interventions that attempt to bolster our antioxidant defenses.
I can see a day when physicians order genotyping on patients at a certain age to determine risk for macular degeneration and put things in place dietary changes, antioxidants, increased screening that could prevent the disease, Canter added. This would be truly personalized medicine.
Canter emphasized that variation in the mitochondrial genome has been linked to a wide variety of diseases including neurodegenerative diseases like Parkinsons and Alzheimers as well as breast cancer and trauma survival.
Its important to realize that theres another genome in the mitochondria, and even though there are not many genes there, theyre important, Canter said.
Source: Vanderbilt University Medical Center