Age-related macular degeneration (AMD) is the leading cause of blindness among older adults in the developed world. To better understand the mechanisms of AMD to hopefully one day prevent and treat it, researchers in the University of Minnesota’s School of Public Health and the Department of Ophthalmology & Visual Neurosciences have developed a unique method for analyzing oxidative damage in tiny amounts of DNA from the human eye. Results of the study were recently published in Scientific Reports.
Led by Irina Stepanov, Ph.D., assistant professor in the School of Public Health and Masonic Cancer Center, University of Minnesota, the team used a highly sensitive method that can detect specific oxidative modifications in DNA. They used this method to analyze mitochondrial DNA from retinal pigment epithelium, a single cell layer from eye tissues, and compared results between samples that came from healthy eyes and those with age-related macular degeneration.
“The outcome of these analyses supports earlier indications that oxidative damage to mitochondrial DNA in retinal pigment epithelium is a potentially important mechanism in the development of age-related macular degeneration,” said Bin Ma, Ph.D., a research associate in the Stepanov laboratory who developed the new methodology. “Most importantly, our study provided a unique tool for future research in this field.”
This new method was needed to analyze DNA from mitochondria, small organelles that serve as “power plants” in cells. The amount of mitochondrial DNA that can be extracted from cells is 100-times lower than the amount of genomic DNA, and retinal pigment epithelium yields only 10-50 nanograms of mitochondrial DNA.
Prior to this work, sensitive and accurate methods for the analysis of specific oxidative DNA modifications, called DNA adducts, in such small amounts of DNA were not available; however, previous studies have indicated oxidative damage to mitochondrial DNA may play a key role in the development of AMD.
Stepanov says this new method can be used for the analysis of DNA from other tissues or from blood, which opens new opportunities for future investigations of this damage in other studies.
“We are planning to analyze additional samples of eye tissues with and without age-related macular degeneration, to confirm the initial indications from this study,” said Stepanov. “This research can help to better understand the role of oxidative mitochondrial DNA damage in age-related macular degeneration and potentially lead to the development of new preventive and treatment strategies.”
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