Photo credit: www.sciencedaily.com
New Insights into Age-Related Macular Degeneration
A collaborative research effort led by the University of California, Irvine, has unveiled that accumulated DNA damage within the retina significantly contributes to age-related macular degeneration (AMD). This finding suggests that focusing on specific retinal cell types may pave the way for treatments aimed at slowing or halting the progression of this debilitating condition.
AMD affects around 200,000 individuals in the United States each year and remains one of the leading causes of vision impairment among people aged 50 and older. The disorder manifests primarily in two forms: the wet variant, which is generally managed with established medical therapies, and the dry variant, for which no effective treatment currently exists.
Detailed in a recent study published in the journal Aging Cell, the researchers explored the detrimental effects of DNA damage—a well-known marker of aging—on retinal function and how it accelerates vision loss.
“Our research emphasizes the vital significance of DNA damage repair in preserving retinal health, which is essential for maintaining good vision,” stated Dorota Skowronska-Krawczyk, a co-corresponding author and associate professor at UC Irvine. “As aging stands as the predominant risk factor for AMD, acquiring deeper insights into the biological processes of aging within the eye is crucial for formulating effective therapies.”
The retina, the light-sensitive tissue located at the back of the eye, requires more oxygen than any other tissue, functioning with the help of the retinal pigment epithelium, which is critical for its performance. Due to its exposure to light and high metabolic demands, the retina is particularly susceptible to oxidative stress and the gradual buildup of DNA damage that accompanies aging. A thorough understanding of the interplay between the retina and the retinal pigment epithelium, as well as the mechanisms behind age-related alterations, is imperative for the development of innovative strategies to address AMD.
In their investigation, the research team compared a mouse model with reduced levels of the ERCC1-XPF enzyme—key for DNA repair—to both young, healthy mice and those showing signs of natural aging. By the age of three months, the modified mice exhibited indicators of visual impairment, structural changes in the retina, irregular blood vessel growth, and altered gene expression patterns alongside metabolic shifts. These findings closely resemble the changes observed in the normal aging process of human eyes.
“A deeper understanding of how DNA damage influences eye conditions like AMD will enable us to devise strategies that tackle the fundamental causes of vision loss. Potential approaches may involve mitigating oxidative stress, boosting DNA repair mechanisms, or eliminating damaged cells before they create adverse effects,” remarked Skowronska-Krawczyk. “Our next steps will focus on identifying which cell types precipitate age-related changes by methodically impairing DNA functions. We aspire to move ahead with the development of preventive strategies that could significantly alleviate the challenges of age-related vision impairment and enhance the quality of life for millions of individuals.”
The research team included William Cho, a project scientist in physiology and biophysics at UC Irvine; co-corresponding author Dr. Laura J. Niedernhofer, a professor and director at the University of Minnesota Institute on the Biology of Aging & Metabolism; as well as collaborations from faculty and students at the University of Minnesota, the University of Florida, and Columbia University.
Source
www.sciencedaily.com