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Research with an Eye Toward Improving Retinopathy Treatment

Professor Julie Busik in her lab

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 findings that have implications for new, noninvasive treatment of diabetic retinopathy and, potentially, other diabetic complications.

The work is focused on cell therapies, specifically on cells involved in vascular or blood vessel repair.

“Vasculature has a very good capacity for repair,” she says. “If you cut yourself, it’s going to heal. The blood vessel will coagulate, a new blood vessel will grow and you won’t know you had that cut several days later.”

The same thing happens in the retina. The repair is made by cell circulating from the bone marrow. These cells, called progenitor cells, are released to make repairs when damage happens.

Diabetes interferes with the body’s ability to repair itself. In the case of diabetic retinopathy, the progenitor cells don’t get released to make the needed retinal repairs. Busik has found that when a subject has diabetes, the progenitor cells have high levels of an enzyme called acid sphingomyelinase.

She used animal models to show that blocking the acid sphingomyelinase enzyme in the bone marrow of diabetic individuals could protect them from retinal inflammation 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 affects the entire body, it’s possible that blocking the enzyme might be beneficial for other diabetic complications.”

Busik’s challenge going forward is to refine the work. While limiting acid sphingomyelinase appears to be beneficial to the progenitor cells in promoting retinal healing and limiting inflammation, it’s 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 she’s looking at could function as a dimmer switch to regulate the acid sphingomyelinase without completely blocking it.

“Delivery of microRNAs is a new field,” 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 Institute of Health is currently supporting several clinical trials that are supporting the principle that it’s possible to take a person’s 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 developing that could offer better ways to inhibit the enzyme,” she notes. “We are trying to first 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 we’ll 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, Julia Busik also carries appointments with the MSU colleges of natural science and human medicine and with MSU AgBioResearch.

Busik’s work is supported by the National Eye Institute, the Juvenile Diabetes Research Foundation and by the Jean P Schultz Endowment.

–Laura Probyn, College of Osteopathic Medicine

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