A group of Australian researchers, including CERA’s Associate Professor Raymond Wong, have identified the involvement of two crucial genes in age-related macular degeneration (AMD). The genes, TMEM97 and POLDIP2, have been found to regulate oxidative stress, which is a significant aspect of macular aging. This discovery, published in both Aging and the International Journal of Molecular Science, provides a more comprehensive comprehension of AMD’s fundamental causes and helps prioritize potential gene targets for future treatments. The study was conducted in collaboration with the University of Melbourne, Lions Eye Institute, and other national partners.
Age-related macular degeneration (AMD) is a major cause of blindness worldwide, yet the mechanisms underlying its development remain unclear. This disease affects the central part of the retina called the macula, which leads to gradual breakdown of cells and distorted central vision. Identifying and comprehending the genes associated with a higher risk of developing AMD can aid researchers in creating treatments that target the root causes of the disease.
Previous studies have already discovered several genes linked to AMD, but Wong’s team is the first to investigate the functions of two specific genes, TMEM97 and POLDIP2, in human retinal pigmented epithelial cells (RPE), the cells affected in AMD.
To examine the genes’ roles, the team established a model of human RPE cells in the laboratory. Using advanced gene editing technology, Wong and his colleagues deactivated the two genes and discovered their essential role in preserving cell health. Genes provide instructions for various biological processes in cells, and by deactivating specific genes, researchers can investigate their functions and determine the role they play.
According to Wong, “It has been discovered that both these genes play a significant role in controlling oxidative stresses, which are crucial mechanisms in the aging of the retina.” Oxidative stress is a natural process in the body that can occur when cells utilize energy. As one ages, the accumulation of oxidative stress in cells leads to damage in many cell types, including RPE. Wong notes that high oxidative stress is generally harmful to cells and may contribute to RPE degeneration.
These results have paved the way for further research into the genetic causes of AMD, as well as the development of future treatments that target genes responsible for cell degeneration. “These discoveries enhance our comprehension of the genes that increase the risk of developing AMD and how the disease progresses,” Wong says. “In the future, studies may focus on these genes to develop treatments for AMD.”