Newly Found Protein and Enzyme Duo May Hold Key to a Cure for Retinopathy


By: Patrick Totty

Thwarting a protein that carries an otherwise benign enzyme into the nuclei of cells in the retina, where the enzyme kills the retinal cells, may hold the key to preventing blindness in patients with diabetes. That’s the conclusion of a two-year study by researchers at Michigan State University seeking a way to treat retinopathy, the disease that often leads to blindness in people with diabetes.

The protein, siah-1, is produced by the body when blood sugar levels are high. Siah-1 then carries an enzyme called GADPH (glyceraldehyde 3-phosphate dehydrogenase) from its normal position in the fluid component of retinal cells directly into the retinal cell nuclei. There, its presence destroys the nuclei and leads to cell death. The discovery of siah-1’s role in retinopathy opens to door to the possibility of a treatment that can stop retinopathy in its tracks, if the protein can be manipulated to prevent it from transporting GADPH into retinal nuclei.

At the beginning of the study, the researchers did not know how cell death is induced in retinopathy, nor did they know about the presence of siah-1 as an abettor of the process. Once they discovered how GADPH works to destroy cells, they had to determine what causes the enzyme to move from its benign location in the cell and become an agent of destruction. Team leader Susanne Mohr, an associate physiology professor at MSU, decided to test for the existence of siah-1 after reading a scientific paper about its relationship with white blood cell death. She was uncertain if the protein even existed in the retina, but wanted to see if she could find it and establish a relationship between it and GADPH. Mohr’s next step will be to see if both siah-1 and GADPH must be present in the retina for cell damage to occur.

An estimated 80 percent of people with diabetes have suffered some damage from retinopathy, ranging from very mild to outright blindness. As type 2 reaches almost epidemic proportions, especially among young people, finding a way to forestall the development of blindness or severe vision problems becomes increasingly urgent. 

The team’s research appeared in the January 29 issue of the Journal of Biological Chemistry.

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