Researchers Identify Two New Genes Associated with AMD

A team of Australian researchers, led by Associate Professor Raymond Wong, the principal investigator of cellular reprogramming at CERA, have discovered the involvement of two significant genes, TMEM97 and POLDIP2, in age-related macular degeneration (AMD). This is the first time these genes have been identified to play a role in regulating oxidative stress, which is a critical factor in the aging of the macula.

The results of the study have been published in two scientific journals, Aging and the International Journal of Molecular Science. These findings have provided a more comprehensive insight into the fundamental causes of age-related macular degeneration (AMD) and facilitated the prioritization of new gene targets for treatment.

This research has been a collaborative effort between several institutions, including CERA, the University of Melbourne, Lions Eye Institute, and other national partners.

Gene Targets

Previous studies have established a link between AMD and multiple genes, however, Associate Professor Raymond Wong's team is the first to explore the functions of the genes TMEM97 and POLDIP2 in human retinal pigmented epithelial cells (RPE), the cells affected in AMD.

To determine the role of these genes, the research team created a human RPE cell model in the lab. By utilizing innovative gene editing technology, the two genes were "turned off" or silenced, leading to the discovery that they play a crucial role in maintaining cell health.

Genes offer instructions for various biological processes within our cells, and by "switching off" certain genes in cells, researchers can examine their effects and discern the roles these genes play.

"It turns out both of these genes play roles in regulating the oxidative stresses, which is a key mechanism in aging of the retina. "As you get older, there's a build-up of oxidative stress in cells, which affects many cell types including RPE," says Wong. "Generally, high oxidative stress is bad for cells—and could contribute to RPE degeneration," Wong says.

Oxidative stress is a natural process in our bodies that can happen when our cells use energy.

The discovery of the roles of TMEM97 and POLDIP2 genes in regulating cell degeneration has presented new possibilities for further research into the genetic causes of AMD. Additionally, it has the potential to lead to the development of new treatments for AMD targeting these specific genes.

Associate Professor Raymond Wong highlights that these findings have contributed significantly to the understanding of the genes that increase the risk of AMD and the disease's progression. He also emphasizes that future research could focus on these genes to develop more effective treatments for AMD.

References:

Tu Nguyen et al, Knockout of AMD-associated gene POLDIP2 reduces mitochondrial superoxide in human retinal pigment epithelial cells, Aging (2023). DOI: 10.18632/aging.204522

Jiang-Hui Wang et al, Development of a CRISPRi Human Retinal Pigmented Epithelium Model for Functional Study of Age-Related Macular Degeneration Genes, International Journal of Molecular Sciences (2023). DOI: 10.3390/ijms24043417