Age-related macular degeneration (AMD) is a serious eye disease that happens when the macula, located near the back of the eye in the middle of the retina, deteriorates over time often leading to loss of central vision.

According to Johns Hopkins Medicine, AMD is the most common reason people over 50 experience severe visual impairment including inability to see colors or fine details, drive a car, or discern faces. There may not be any early signs or symptoms.

Recently, Australian researchers found possible genetic clues to how AMD may form that could lead to earlier diagnosis and better treatment.*

What the researchers did

Investigators from four Australian research institutions, led by the Garvan Institute of Medical Research, used stem cells in an innovative approach to study the development of AMD. For this study:

• 43 study participants with late-stage AMD and 36 healthy controls provided skin samples
• The skin cells were turned back into basic stem cells, then re-engineered into specialized retinal pigment epithelium (RPE) cells that are affected by AMD.
• The genetic development of the cells was compared between the two groups.

Lining the back of the eye, RPE cells are vital to protecting the health and function of the retina. The deterioration of these cells appears to lead to the death of photoreceptor cells.  Photoreceptors are nerve cells that gather light and transmit visual information to the brain. Without these cells, vision loss occurs.

What they found

The investigators’ model of AMD, consisting of 127,600 RPE cells, revealed genetic clues to the disease’s development, including:

• 439 genetic markers of AMD, 
• 43 of which are possible new gene variants.

Potential ways for AMD to occur were identified and tested in the cells. Interestingly, the researchers found differences between diseased and healthy RPEs in the cells’ mitochondria, the power centers that produce cells’ energy.

What it means

The findings, published in Nature Communications, show mitochondrial proteins as potential treatment targets for AMD. The newly discovered markers can already be used to test the effectiveness of AMD treatments on patient cells in a lab. 

“Ultimately, we are interested in matching the genetic profile of a patient to the best drug for that patient,” said co-lead study author Alice Pébay, Ph.D. “We need to test how they work in cells relevant to the disease.” 

“We’ve tested the way that differences in people’s genes impact the cells involved in age-related macular degeneration,” added co-lead author Joseph Powell, Ph.D., Garvan Institute’s Pillar Director of Cellular Science. “This is the basis of precision medicine, where we can then look at what therapeutics might be most effective for a person’s genetic profile of disease.”

Pébay, Powell, and study co-author Alex Hewitt, Ph.D., MBBS recently uncovered genetic markers for glaucoma using a similar stem cell approach.

The exact causes of AMD are still unclear, though the evidence for a combination of genetics and environment is strong. Risk factors for AMD include:

• Age, 
• Family history, and
• Smoking.

*Garvan Institute of Medical Research. (2022, July 26). Clues to age-related macular degeneration revealed. https://www.sciencedaily.com/releases/2022/07/220726093642.htm