Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss in the United States. Despite existing treatments, the underlying causes and effective treatments for this disease remain elusive. A new study published in the journal Developmental Cell provides important insights into the cellular mechanisms behind AMD and offers a potential path to new treatments.
“Current AMD treatments have limited efficacy and are often associated with significant side effects,” said Ruchira Singh, Ph.D., of the University of Rochester’s Fraum Eye Institute and Center for Vision Sciences, and lead author of the study. said. “Our research aims to identify new therapeutic targets that may halt the progression of this disease.”
TIMP3: a key protein in the development of AMD
This study used human stem cells to model AMD, overcoming the limitations of previous studies using animal models. By examining genes associated with both AMD and a rare inherited form of blindness called macular dystrophy, researchers identified key proteins involved in the early stages of the disease.
The retinal pigment epithelium (RPE), the cell layer at the back of the eye, plays a key role in AMD. Over time, lipid and protein deposits known as drusen build up in the RPE. These deposits are often early indicators of AMD.
Researchers discovered that a protein called tissue metalloproteinase 3 inhibitor (TIMP3) is overproduced in AMD. TIMP3 inhibits the activity of enzymes called matrix metalloproteinases (MMPs), which are essential for eye health. Reduced MMP activity increases other enzymes that promote inflammation and drusen formation.
Dr. Sonal Dalvi and Dr. Ruchira Singh are co-authors of a new study on age-related macular degeneration published in the journal Developmental Cell.
Targeting inflammation: a new approach to preventing drusen formation
By using small molecule inhibitors to block the activity of enzymes associated with inflammation, researchers were able to reduce drusen formation in the model, suggesting that targeting this pathway could be used to prevent AMD. It was suggested that this could be a promising strategy.
“The cellular pathways involved in drusen formation are key drivers of AMD progression,” said Dr. Singh. “If we can stop the accumulation of drusen, we may be able to prevent the disease from progressing to the stage where vision loss occurs. This research could change the lives of millions of people living with AMD. It gives us hope that we can develop new treatments that can provide significant improvements.”
Other co-authors include Sonal Dalvi, Michael Roll, Amit Chatterjee, Lal Krishan Kumar, Akshita Bhogavalli, Nathaniel Foley, Cesar Arduino, Whitney Spencer, co-author with University of Rochester, Cheyenne Reuben Thomas, David They include Ortolan, Kapil Bharti National Institute of Science. Alice Pevey of the Eye Institute, University of Melbourne, and Vera Anand Apte of the Cleveland Clinic. This research was supported by the National Eye Institute, ForeBatten Foundation, and Research to Prevent Blindness.
