When it comes to many diseases, particularly eye diseases, genetics plays a role in the how and when a specific disease develops. Of course, it isn’t as simple as having X gene and getting Y disease. Lifestyle factors can influence certain genes. Also, the presence of modifier genes—genes that are slightly different, such as a single nucleotide change that varies from its usual sequence—can affect disease development.
How can knowledge about genetics lead to a better understanding of eye disease and, ultimately, treatments that improve outcomes? Scientists are studying how genetics contribute to eye disease, and here is that they have learned.
Age Related Macular Degeneration & Genetics
Age related macular degeneration is an eye disease that involves a combination of factors, such as genetics, age and lifestyle. Smoking increases the risk of getting age related macular degeneration, while eating foods that have omega 3, such as salmon, decreases its risk. As for the genetics that lead to this disease, 52 DNA variants have been identified. These DNA variants are non-coding, so many questions remain about variants influence the development of age-related macular degeneration.
Scientists at the National Eye Institute at the National Institutes of Health studied 160 retinas from donors who had age related macular degeneration. They found 87 target genes where a mix of environmental factors may influence a person’s risks of developing the disease. The target genes located in areas where the processes that regulate the expression of the genes we are born with—known as epigenetic mechanisms—contribute to whether someone develops age-related macular degeneration or not.
The donor retinas were studied for their specific genetic makeup, messenger RNA (which deals with gene expression), the presence of genetic variants, the three-dimensional structure of its DNA, and profiles of DNA methylation, a vital epigenetic mechanism. DNA methylation is crucial because it turns genes “off” by either recruiting proteins that repress gene expression or by impeding the binding of transcription factors to DNA, which is important for protein production.
The DNA methylation patterns are set during fetal development, acting as a switch that generates different types of proteins. Environment factors throughout our lifetime, such as UV exposure, diet, and exercise, can disrupt these patterns and lead to changes in gene expression. Additionally, changes in gene expression can lead to changes in DNA methylation, and non-coding genetic variants also influence DNA methylation patterns, both independently and in connection with environmental exposure.
The findings provide a basis for treatments aimed at regulating the gene-environment relationship and its contribution to age-related macular degeneration. The finding also reveal the involvement of mitochondria and cellular processes, such as oxygen utilization for energy production and protein regulation within cells, in the development of age-related macular degeneration through changes in gene expression.
What if a modifier gene is causing all the trouble? That will be covered in Part Two of this blog entry.
Source:
https://www.nei.nih.gov/about/news-and-events/news/nei-study-points-ground-zero-amd-development