A BrightFocus-funded research team has identified, for the first time, how antioxidants may be used to treat people with certain variants of genetic risk factors for age-related macular degeneration (AMD). Understanding the connection between gene variations and antioxidants could lead to targeted therapies to treat or even help prevent the disease.
The study, led by Macular Degeneration Research grantee Ya-Ju Chang, PhD, of Columbia University Medical Center in New York, focused on the retinal cells of people with the ARMS2/HTRA1 gene, which puts them at higher risk of age-related macular degeneration and of developing it at an earlier age.
The researchers found that the antioxidant sodium phenylbutyrate reduced oxidative stress in retinal cells of people with ARMS2/HTRA1-related macular degeneration. Oxidative stress plays an important role in the development of AMD by damaging cells in the eye. Antioxidants prevent or reduce the damage it causes.
The study used stem cells from the retinas of people with high-risk genes and higher oxidative stress levels. The cells were manipulated using clustered regularly interspaced short palindromic repeats (CRISPR) genetic editing to isolate the effect of individual variants to increased oxidative stress in AMD. Sodium phenylbutyrate was shown to reverse the cell damage.
The results were published in Proceedings of the National Academy of Sciences, a journal that serves as an authoritative source of original research in the biological, physical, and social sciences.
The antioxidant in the study was sodium phenylbutyrate, a salt approved for clinical use that comes from a type of fatty acid. However, other types of antioxidants are found in foods like berries, nuts, and green vegetables, which are important for overall good health. Eating a well-balanced diet of eye-healthy foods that are enriched in vitamins and minerals may lower the risk of AMD.
An example of antioxidants widely used to counteract oxidative stress in AMD is the AREDS 2 formula, a special dietary supplement that can help slow down vision loss. Antioxidants for AMD treatment help to prevent the death of retinal pigment epithelium cells, where macular degeneration begins, and decrease oxidative stress.
Sodium phenylbutyrate, an agent with antioxidant activity, is an FDA-approved drug used to treat rare genetic conditions known as urea cycle disorders by helping to reduce high levels of ammonia in the blood.
Genetics and Age-Related Macular Degeneration
AMD is believed to develop due to a combination of genetic and environmental factors, such as age and high blood pressure. In some cases, it can run in families. Up to 20% of people with AMD have at least one first-degree relative, such as a parent or sibling, with the condition.
Researchers have considered genetic changes as possible risk factors. Changes on a chromosome in a region known as 10q26 are strongly linked to increased AMD risk. The 10q26 region contains ARMS2 and HTRA1, the two genes that were part of this unique research study.
Changes in both genes have been studied as possible risk factors for the disease. However, because the two genes are so close together, it’s hard to tell which gene is associated with the risk of AMD or whether the increased risk comes from variations in both genes.
Genetic testing for AMD is available, but there currently isn’t much to do with the information other than to recommend steps to reduce risk, such as not smoking, eating a diet rich in fruits and vegetables, and eating fish twice a week.
However, if targeted treatments such as antioxidants therapy are available in the future, knowing about certain genetic variants may become important. Learn more about genetic testing for AMD.