Modeling the most common form of vision loss in older adults
A new model of age-related retinal degeneration will give researchers a deeper understanding of the disease, as well as possible ways to prevent or treat it
UNIVERSITY OF PENNSYLVANIA
Age-related macular degeneration (AMD) affects roughly 200,000 individuals in the United States each year. In most, it comes on slowly, gradually blurring the central field of vision used for activities like reading and driving. While treatments exist to slow its progression, there is no cure.
A team led by Kathleen Boesze-Battaglia of the University of Pennsylvania has now characterized a new animal model that mimics aspects of AMD, in particular in how lipids are handled in the eye. Recapitulating many aspects of the human disease, 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.
“Currently for the most prevalent form of AMD, dry AMD, you can slow it down a little bit, but you can’t really cure it,” says Boesze-Battaglia, professor in the Department of Biochemistry in Penn’s School of Dental Medicine. “And 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. That then allows you to consider how you could therapeutically target those steps.”
A defining characteristic of dry AMD is the accumulation in the eye of what are known as drusen, small lipid-filled deposits. These arise because of a defect in processing the lipid-rich outer segments of the retina’s photoreceptor cells, those that are responsible for vision.
In earlier studies, Boesze-Battaglia and other researchers examined how the retinal pigment epithelium (RPE), the layer of cells that ingest shed outer segments from the photoreceptors, metabolizes lipids.
“This outer segment, the tip of the photoreceptor, it’s like a hamburger without a bun,” says Boesze-Battaglia. “It’s a very lipid-rich sack.”
They found that this digestion process, known as phagocytosis, 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 was able to use a mutant mouse lacking LC3B to assess the effects the loss on visual function….