Age-related macular degeneration (AMD) is a leading cause of vision loss in the elderly, affecting the macular region of the retina at the back of the eye. The two major forms of AMD are wet (neovascular) and dry (atrophic). (See figure 1. below) Between the ages of 66 and 74, approximately 20 percent of the population has some form of AMD; by ages 75-85, that increases to 35 percent to 40 percent of the population. 
Unfortunately, damage associated with AMD affects central vision, compromising the ability to read and see details; it can ultimately lead to severe vision loss. (See figure 2 below.) There are two categories of risk factors for AMD: those factors over which you have no control, including aging, family history, gender, race and genetics; and those factors you can control, such as smoking, obesity, eating habits and exercise patterns. Recent studies have demonstrated that genetics are associated with the development and progression of AMD. 
To study genetics, one must examine the DNA of individuals, which is critical for determining how a cell functions. (See figure 3 below) However, there are two different types of DNA in everyone. The one we know the most about is nuclear DNA (nDNA), which is inherited half from the mother and half from the father and accounts for more than 20,000 genes. The other DNA is mitochondrial DNA (mtDNA), which is small and codes for only 37 genes. It is inherited only from the mother with no contribution from the father. Even though the mtDNA is small, it is very important for healthy cells, because mitochondria provide the energy for the cell in the form of adenosine triphosphate (ATP) molecules. If the mitochondria do not function well or the mtDNA are damaged, the cell will die. An analogy is that mitochondria are like batteries within a flashlight: If the batteries are bad, the flashlight will not work. It has been proposed that the loss of mitochondria and mtDNA plays an important role in causing dry AMD. 
The DEF-supported retinal genetics laboratory at University of California, Irvine, directed by Dr. Cristina Kenney, has investigated five different nuclear genes associated with AMD. In addition, they have shown that individuals and families with specific mtDNA patterns have higher risks of developing AMD, demonstrating that multiple genes are important in the disease. The retinal genetics laboratory will be examining more than 600 additional DNA samples from AMD subjects to be compared to 600 normal, non-AMD individuals. The DNA patterns for each patient will be analyzed with sophisticated, rapid methods that can screen for gene defects within a few days. This type of analysis used to take weeks to perform, but the retinal genetics laboratory has state-of-the-art technology that allows hundreds of samples to be analyzed in a short period. Kenney's group will be investigating which nuclear genes and mitochondrial genes are involved with AMD, as well as whether there are additive, harmful effects between the genes and environmental factors such as smoking. These genetics studies are helping us identify patients at higher risk for developing AMD, to provide a rationale for therapeutic interventions, to develop gene therapies to replace defective genes to prevent AMD, and to tailor the most effective therapies for AMD patients. The AMD genetics project requires support for a full-time technician ($75,000/year), molecular tests ($10,000/year) and genetic sequencing tests ($15,000/year). This work involves collaboration among different laboratories throughout the United States, including UCLA, University of Minnesota, University of Pittsburgh, Children's Hospital of Philadelphia and multiple ophthalmologists in Southern California. Results from this research will be presented at national and international meetings, as well as published in top-ranked journals and books. This important discovery-stage research is an essential building block in understanding the strong role genetics plays in the development and progression of AMD.
Posted January 2012