Researcher examines protein's role in diabetic retinopathy

June 7th, 2012
A Wayne State University researcher believes a protein that fails to reach the nucleus of retinal cells may play a role in causing eye disease in people with diabetes.

Renu A. Kowluru, Ph.D., professor of ophthalmology, anatomy/cell biology and endocrinology at Wayne State University and the Kresge Eye Institute, recently received a one-year, $110,000 Innovative Grant from the Juvenile Diabetes Research Foundation to help gain new insight into the development of diabetic retinopathy and identify targets for future therapeutic interventions.

Her hypothesis is that NF-E2-related factor 2 (Nrf2), a protein that regulates antioxidant response, fails to reach to the nucleus of cells in the retina to neutralize free radicals, which are volatile. As a result, Kowluru said, KEAP1 - the protein that serves as an anchor for Nrf2 and represses its activation - increases, damaging the mitochondria, the cells' power source. That damage, she believes, in turn accelerates the death of cells in tiny blood vessels (capillaries), ultimately resulting in the development of retinopathy.

Diabetes is a leading cause of acquired blindness in young adults. Almost 50 percent of diabetes patients have some form of retinopathy - not necessarily blindness - after nine years, and that figure increases to 95 percent after 20 years of the disease.

"Basically it doesn't leave any diabetic patient," Kowluru said.

Titled "Role of Nrf2-KEAP1 in Diabetic Retinopathy," her project will look at the oxidative stress, an imbalance between the production and utilization of free radicals, in an effort to determine how a disease state - diabetes in this case - causes that imbalance.

"We have shown that in diabetes, mitochondria are damaged, and when they are damaged they initiate cell death," Kowluru said. "We want to see what the role of Nrf2 is in initiating this signal."

Beginning in October, her team will genetically regulate Nrf2 to examine the temporal relationship between the failure of the protein to reach cells' nuclei and the signal sent by damaged mitochondria that triggers cell death. She hopes to determine if the former event precedes the latter, or if they occur at the same time.

Additionally, Kowluru will examine the point on the gene where Nrf2 and KEAP1 interact to determine whether diabetes induces epigenetic changes in Nrf2, impairing its binding with KEAP1.

Because epigenetic changes, which are functionally relevant modifications to the genome that do not involve a change in the DNA sequence, can be passed along to future generations, prevention becomes an even more important goal, she said. Drugs now in the clinical trial stage for other chronic diseases (e.g., cancer) may be able to prevent epigenetic changes in the retina.

"Once we understand the problem, we can administer supplements and prevent the downstream pathway for retinopathy," Kowluru said.

Provided by Wayne State University

This Phys.org Science News Wire page contains a press release issued by an organization mentioned above and is provided to you “as is” with little or no review from Phys.Org staff.

More news stories

Peacock's train is not such a drag

The magnificent plumage of the peacock may not be quite the sacrifice to love that it appears to be, University of Leeds researchers have discovered.

US experts skeptical of testosterone drug benefits

U.S. health experts say there is little evidence that testosterone-boosting drugs are effective for treating common signs of aging and large studies are needed to support their continued use in millions of American men.

NASA releases IRIS footage of X-class flare (w/ Video)

On Sept. 10, 2014, NASA's newest solar observatory, the Interface Region Imaging Spectrograph, or IRIS, mission joined other telescopes to witness an X-class flare – an example of one of the strongest solar flares—on ...

Space: The final frontier... open to the public

Historically, spaceflight has been reserved for the very healthy. Astronauts are selected for their ability to meet the highest physical and psychological standards to prepare them for any unknown challenges. However, with ...

Study: Americans endure unwanted care near death

Americans suffer needless discomfort and undergo unwanted and costly care as they die, in part because of a medical system ruled by "perverse incentives" for aggressive care and not enough conversation about what people want, ...

NASA sees Tropical Storm Polo intensifying

Tropical storm warnings now issued for a portion of the Southwestern coast of Mexico as Polo continues to strengthen. Infrared imagery from NASA's Aqua satellite showed powerful thunderstorms around the center ...