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Foundation-funded researchers are developing an elegant approach to wiping out the toxic, vision-robbing molecules common to many retinal degenerative diseases. They hope to turn their emerging research into a cross-cutting treatment that has the potential to preserve vision in people with a broad range of retinal conditions. Whether a person is affected by retinitis pigmentosa, macular degeneration or another retinal degenerative disease, they likely have an abundance of harmful byproducts in their retinas because of the tissue’s diminished capacity to process oxygen. Known as reactive oxygen species (ROS), these molecules destroy photoreceptors and lead to vision loss. Experts believe the rate of destruction and vision loss often gets worse as the disease advances, because the retina processes less and less oxygen leading to more and more toxic ROS.James McGinnis, Ph.D., a Foundation-funded researcher from the University of Oklahoma Health Sciences Center, is leading the development of an innovative nanoparticle-based treatment that preserves vision by “gobbling up” the toxic ROS in the retina. He and his colleagues have demonstrated the effectiveness of their approach in mouse models of Usher syndrome and wet age-related macular degeneration (AMD). The treatment involves the injection of cerium oxide nanoparticles — particles that are 1/12,000th the diameter of a human hair. Called nanoceria, the particles devour ROS in the retina, thereby slowing photoreceptor degeneration and preserving vision. Cerium dioxide is a compound that has strong oxygen consumption properties, especially when used in nanoparticle form. In the mouse model of wet AMD, nanoceria also inhibited the production of vascular endothelial growth factor (VEGF), a protein that can lead to the proliferation of leaky, vision-robbing blood vessels. The treatment even cleared up retinas already stricken with the unhealthy blood vessels. Dr. McGinnis says that a key benefit of nanoceria is their sustained effect as a treatment because they can regenerate and keep working over a long period of time. He notes that more research is needed to better determine how long a single treatment will last, but he believes that an injection of nanoceria might be effective for several months or more. While the retina is a thin, fragile piece of tissue, it also has the highest rate of oxygen metabolism of any tissue or organ in the body, and therefore undergoes substantial oxidative stress, even when healthy. Exposure to bright light, which is damaging, especially over time, is a major factor contributing to oxidative stress in the retina. Other factors such as smoking and an unhealthy diet can contribute to oxidative stress throughout the entire body, and are considered risk factors for AMD. ROS are thought to be major destructive culprits in a variety of retinal degenerative diseases, as well as other degenerative neurological conditions such as Alzheimer’s disease, amyotrophic lateral sclerosis (ALS or Lou Gehrig’s disease), and Parkinson’s disease. “Dr. McGinnis’s work highlights why lab research remains so critical. The project is at an early stage, but this novel approach shows a lot of potential to help people regardless of their retinal condition,” says Stephen Rose, Ph.D., chief research officer, Foundation Fighting Blindness. “This is a great example of why the Foundation is committed to aggressively funding basic and lab-based translational science. We always have to be thinking ahead.” Dr. McGinnis’s work on nancoeria was published in the journals Public Library of Science ONE (PLoS ONE), February 22, 2011, and Neurobiology of Disease, March 29, 2011. |
