image: Graphic about research and grant.
Credit: University of Oklahoma
OKLAHOMA CITY – It’s an unfortunate fact of aging: Live long enough and, eventually, reading this sentence will get difficult, even impossible. Three in 10 Americans older than 80 have some form of age-related macular degeneration (AMD), while for Oklahoman octogenarians, it’s closer to 50%.
Now, new research from the University of Oklahoma aims to illuminate the causes of AMD and help clinicians peer into a black box of blindness.
With support from a four-year, $1.7 million grant from the National Institutes of Health, Jiyang Cai, Ph.D., a professor of biochemistry and physiology at the OU College of Medicine, is studying how cells in the retina communicate and whether the messages they send could be programmed to treat or slow AMD, the leading cause of adult blindness.
Cai and colleagues believe one trigger for AMD occurs when a tiny molecule, called microRNA-204, is no longer able to message the gene that regulates lipids in retinal microglia cells, which help maintain immune function in the eye.
“When we see more lipids in the microglia, we know that something is wrong,” Cai said. “It means that the microglia aren’t doing their job.”
To determine how the breakdown occurs, Cai and colleagues are mapping the links between cells and genes in the eyes of laboratory mice.
Age-related macular degeneration begins with weakening of retinal pigment epithelium cells (RPEs), a layer of cells that support the retina’s photoreceptors. When degeneration occurs, the affected tissues call in immune cells to clear the metabolic products, which in turn triggers chronic inflammation.
In published and preliminary studies, Cai has determined that RPE cells send signals via miRNA to microglia by using extracellular vesicles (EVs), tiny delivery vans that transport packages of information.
The research team also found that microRNA-204 targets the Tgfbr2 gene in microglia, which is involved in inflammation and fat metabolism.
They are now trying to understand is whether extracellular vesicles from RPE cells can be used or engineered to rejuvenate aging retinal microglia. In other words, perhaps the delivery vans can be programmed to carry cargo that is beneficial to the retina.
“We want to figure out how microRNAs in these extracellular vesicles interact inside the microglial cells, which might provide a mechanism for future treatments,” Cai said.
“Until now, we’ve just watched something get fed into a black box and done a readout of what comes out,” he said. “With this research, we’re trying to understand how cargo contents within EVs might contribute to the therapeutic effects of these vesicles.”
Cai said the results of these studies will provide insights into how EVs and their associated cargoes interact with two distinct cell types in the outer retina. The findings could also guide future applications of EV-based delivery of compounds to modulate microglia function and alleviate the progression of age-related retinal diseases.
If successful, the strategy would be a welcome departure from current therapies. For patients with dry macular degeneration, the most common form of the disease, treatment includes injecting antibodies directly into the eye.
Unfortunately, these treatments are only about 10-15% effective at slowing the progression of the disease, Cai said. There are currently no treatment options for many of the patients with late-stage AMD.
Still, as promising as the work is, Cai said it won’t turn back time. Weaker vision is simply a part of getting older.
“We’re looking to slow the progression of the degeneration rather than preventing it from happening,” he said. “Everybody will get some kind of degeneration with aging. But maybe we can turn it into a minor annoyance rather than a life-changing eventuality.”
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About the Project
The research reported in this news release is supported by the National Eye Institute, a component of the National Institutes of Health, under award number R01EY035855-01A1. The content of this news rlease is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
About the University of Oklahoma
Founded in 1890, the University of Oklahoma is a public research university with campuses in Norman, Oklahoma City and Tulsa. As the state’s flagship university, OU serves the educational, cultural, economic and health care needs of the state, region and nation. In Oklahoma City, OU Health Sciences is one of the nation’s few academic health centers with seven health profession colleges located on the same campus. OU Health Sciences serves approximately 4,000 students in more than 70 undergraduate and graduate degree programs spanning Oklahoma City and Tulsa and is the leading research institution in Oklahoma. For more information about OU Health Sciences, visit www.ouhsc.edu.