Study Finds the Cause of Blindness from Diabetes

The damage occurs in the eye's blood vessels, but researchers were unsure why or how those cells became impaired. The leading cause of young adult blindness is caused by diabetic retinopathy -- it's time to help find a cure or a treatment for diabetic patients say these researchers.

The research reveals that when blood sugar levels are high, the siah-1 protein is produced. The siah-1 protein helps move another protein, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), into the nucleus of Muller cells. Muller cells have direct contact with blood vessels in the eye. The Muller cells die when GAPDH accumulates in their nuclei, which eventually leads to the vascular damage connected to blindness.

Susanne Mohr, MSU associate professor of physiology stated "But we weren't sure how the GAPDH was getting in there. It doesn't contain any of the necessary signaling motifs. I read about the siah-1 protein and cell death in white blood cells in a Nature paper, so we decided to investigate them. We had no idea if the siah-1 protein was even in the retina."

Stopping GAPDH from moving into Muller cell nuclei therefore, is important to stopping the progress of diabetic retinopathy. GAPDH does continue to accumulate in Muller cell nuclei even after blood glucose levels are lowered or stabilized, forcing the retinal damage to continue, only more slowly.

"If we can keep GAPDH out of the nuclei, we may be able to completely stop diabetic retinopathy," Mohr said. "Our next step is to figure out if both the GAPHD and the siah-1 proteins have to be together in a complex to cause cell death."

Eventually, this could lead to the ultimate goal of treatment. Around 40 percent to 45 percent of patients with diabetes suffer from diabetic retinopathy, making the research viable and necessary to their quality of life.

Journal of Biological Chemistry, Feb. 2010