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SUMMER 2016 COMMUNIQU 9 FACULTY by Laura Probyn According to the National Eye Institute diabetic retinopathy is the most common diabetic eye disease and a leading cause of blindness in American adults. There are roughly 7.7 million adults with the disease in the U.S. and 93 million worldwide. While there are currently treatment options for those suffering with diabetic retinopathy they are very invasive one requires monthly eye injections and can mean loss of night vision and peripheral vision. MSU Associate Professor of Physiology Julia Busik and her team recently published two papers one in the journal Stem Cells and another in PLOS ONE that describe ndings that have implications for new noninvasive treatment of diabetic retinopathy and potentially other diabetic complications. The work is focused on cell therapies specically on cells involved in vascular blood vessel repair. The vasculature has a very good capacity for repair she says. If you cut yourself its going to heal. The blood in the vessel will coagulate a new blood vessel will grow and you wont know you had that cut several days later. The same thing happens in the retina. The repair is made by cells circulating from the bone marrow. These cells called progenitor cells are released to make repairs when damage happens. Diabetes interferes with the bodys ability to repair itself. In the case of diabetic retinopathy the progenitor cells have decreased membrane uidity making most of the cells unable to squeeze out of the bone marrow into circulation. Even the progenitors that do get released have reduced ability to home into places where repairs are needed. Busik has found that when a person has diabetes the progenitor cells have high levels of an enzyme called acid sphingomyelinase leading to higher levels of very rigid lipid ceramide in the membranes thus reducing membrane uidity. She worked with MSU Professor of Chemistry Gary Blanchard to measure the progenitor cells membrane uidity and used animal models to show that blocking the acid sphingomyelinase enzyme in the bone marrow of diabetic individuals could protect them from retinal inammation and damage. By just blocking acid sphingomyelinase in the bone marrow cells we could treat the eye and make it healthy she points out. The Stem Cells paper examined diabetic retinopathy but because bone marrow IMPROVING RETINOPATHY TREATMENT A VISION FOR SAVING SIGHT affects the entire body its possible that blocking the enzyme might be benecial for other diabetic complications. Busiks challenge going forward is to rene the work. While limiting acid sphingomyelinase appears to be benecial to the progenitor cells in promoting retinal healing and limiting inammation its not an enzyme that can be completely blocked as doing so can bring on neurodegenerative disease. She will be using microRNA a type of molecule that controls gene expression to limit the enzyme. The microRNA shes looking at could function as a dimmer switch to regulate the acid sphingomyelinase without completely blocking it. Busiks work is supported by the National Eye Institute the Juvenile Diabetes Research Foundation and the Jean P. Schultz Biomedical Research Endowment. Images showing the effect of diabetic retinopathy left on incorporation of bone marrow-derived cells green into retinal microglia and blood vessels red. Delivery of microRNAs is a new eld Busik notes. There are several labs looking at ways to deliver them and to target them to the tissue where you want to have an impact. At the same time that Busik is looking at cell transfer therapies the National Institutes of Health is currently supporting several clinical trials based on the principle that its possible to take a persons blood sample isolate the progenitor cells and grow them in a lab and then replace them into the patient and show improved healing. There are some new delivery mechanisms that are being developed that could offer better ways to inhibit the enzyme she notes. We are trying to rst prove that using the microRNA will work as well as just knocking out the acid sphingomyelinase but better because it will not have all of the side effects. In the future well want to see if we can collaborate with the labs working on the delivery mechanisms. In addition to her appointment with the MSU College of Osteopathic Medicine she also carries appointments with the MSU colleges of natural science and human medicine and with MSU AgBioResearch.