Penn Dental Medicine Study Models Age-related Macular Degeneration
PHILADELPHIA, Dec. 20, 2018 /PRNewswire/ -- Age-related macular degeneration (AMD) affects roughly 200,000 individuals in the U.S. annually. In most, it comes on slowly, gradually blurring the central field of vision. While treatments exist to slow its progression, there is no cure.
A team led by Dr. Kathleen Boesze-Battaglia of Penn Dental Medicine has now characterized a new animal model that mimics important features of AMD, in particular, how lipids are handled in the eye. The model will help researchers probe the environmental risk factors that promote the condition, and eventually perhaps help them craft a successful treatment. They reported their findings in Frontiers in Cellular Neuroscience.
"You can slow down the most prevalent form of AMD, dry AMD, t, but you can't really cure it," says Boesze-Battaglia. "That's why these models are particularly valuable. They take a defect in a normal physiological process and allow you to find the important regulatory steps to therapeutically target."
A defining characteristic of dry AMD is the accumulation in the eye of small lipid-filled deposits. These arise because of a defect in processing the lipid-rich outer segments of the retina's photoreceptor cells responsible for vision.
In earlier studies, Boesze-Battaglia examined how the retinal pigment epithelium, the layer of cells that ingest and shed outer segments from the photoreceptors, metabolizes lipids.
They found that this digestion process is accomplished with assistance from a group of proteins in the microtubule-associated protein 1 light chain 3 (LC3) family. After finding a protein that bound to one of these family members, LC3B, the Penn-led group used a mutant mouse lacking LC3B to assess the effects the loss has on visual function.
Using non-invasive imaging, they observed that older mice with the mutation had abnormalities in their retinas, indicative of dysfunction.
"The most severe results were in mice over 20 months old," Boesze-Battaglia says. "You saw the lipid deposits, increased inflammation, increased immune cell infiltration, increases in inflammatory compounds, and a loss of function."
With a useful animal model, the researchers hope to further investigate both risk factors and possible therapies for AMD. In addition, the model gives scientists a way to evaluate the therapeutic utility of compounds that enhance the lipid-clearing process.
The study was supported by the NIH (grants EY010329, EY026525, EY001583, EY005121, GM103340, EY025585, VX002340, and EY012951), Veterans Affairs Research Career Scientist program, and Eye, Ear, Nose, and Throat Foundation.
CONTACT: Beth Adams, 1-215-573-8224, [email protected]
SOURCE Penn Dental Medicine
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