A research team in the United States has discovered that accumulated DNA damage in the retina is a key contributor to age-related macular degeneration and that targeting specific retinal cell types may lead to treatments that slow or stop progression.
The study, co-led by the University of California, Irvine, looked into AMD, a major cause of blindness in people over 50 and believed to affect about 1.5 million Australians, according to the Macular Disease Foundation Australia.
It exists in two forms: wet, which is treated with well-established therapies, and dry, which lacks effective remedies.
A media release from the university said the research, recently published online in the journal Aging Cell, reveals how DNA damage, a hallmark of aging, “compromises the retina’s function and accelerates vision loss”.
“Our findings highlight the critical role DNA damage repair plays in maintaining retina health for good vision,” said Associate Professor Dorota Skowronska-Krawczyk co-corresponding author and UC Irvine associate professor of physiology and biophysics.
“Because age is the strongest risk factor for AMD, gaining deeper insights into the underlying biology of aging in the eye is essential for developing effective therapies.”
The retina, a light-sensitive tissue at the back of the eye, consumes more oxygen than any other tissue in the body and relies on the retinal pigment epithelium cell layer to function properly.
The release said its exposure to light and intense metabolic activity makes it highly vulnerable to oxidative stress and the accumulation of DNA damage over time, a process closely linked to aging.
Understanding the delicate relationship between the retina and the retinal pigment epithelium and the basic mechanism driving age-related changes was crucial for developing new approaches to combat AMD, said the release.
The team compared a mouse model with reduced levels of ERCC1-XPF, a DNA repair enzyme, with both young, healthy mice and naturally aging mice. By just 3 months of age, the model showed signs of visual impairment, structural alterations in the retina, abnormal blood vessel formation, and shifts in gene expression and metabolism, as well as mitochondrial dysfunction in the retinal pigment epithelium. All these changes mirror those seen in natural human eye aging.
“The more we know about how DNA damage contributes to eye diseases like AMD, [the better] we can develop interventions that address the root causes of vision loss,” said A/Prof Skowronska-Krawczyk.
“These could include strategies to counteract oxidative stress, enhance DNA repair or even remove damaged cells before they cause harm.”
She said the team now planned to investigate which cell types drive age-related changes by selectively impairing DNA mechanisms.
“Our goal is to advance the development of preventative interventions that significantly reduce the burden of age-related vision loss and improve the quality of life for millions.”
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