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The research is published in the Jan. 29, 2010 issue of the Journal of Biological Chemistry. "Our earlier research showed that high glucose levels cause GAPDH to accumulate in the nuclei of Müller cells in the retina," Mohr explained. "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." Mohr's research also found that lowering levels of siah-1 proteins stopped GAPDH from moving into the nuclei of Müller cells, which stopped them from dying. "This is very exciting," Mohr said. "We know that we can't regulate production of GAPDH because it's necessary for producing energy throughout the body. But since siah-1 is produced only when glucose levels are high, regulating it doesn't cause any problems. If we can figure out how to stop siah-1 production, it may lead to new treatments for diabetic retinopathy." Mohr explained that stopping GAPDH from moving into Müller cell nuclei is important to halting the progress of diabetic retinopathy. However, even after glucose levels are lowered and stabilized in diabetics, GAPDH continues to accumulate in Müller cell nuclei. So the retinal damage keeps worsening, just 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." E. Chepchumba Yego, doctoral student at Case Western Reserve University, is co-author of the paper. Mohr began the research at Case Western and then continued the project when she joined MSU in August 2009. The research is funded by the National Institutes of Health and supported by the Michigan Agricultural Experiment Station.
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