Researcher identifies cell mechanism leading to diabetic blindness

February 1, 2010

Scientists have long known that high blood sugar levels from diabetes damage blood vessels in the eye, but they didn't know why or how. Now a Michigan State University scientist has discovered the process that causes retinal cells to die, which could lead to new treatments that halt the damage.

Diabetic retinopathy is a common side effect of diabetes and the leading cause of blindness in young adults in the United States. It's estimated that between 40 percent and 45 percent of people diagnosed with diabetes have some degree of diabetic retinopathy.

Research by Susanne Mohr, MSU associate professor of physiology, found the siah-1 protein is produced by the body when blood sugar levels are high. She then discovered that the siah-1 protein serves as a type of chauffeur for another protein, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), shuttling the GAPDH into the nucleus of Müller cells, special cells that have contact with the blood vessels in the eye. When GAPDH accumulates in their nuclei, the Müller cells die, which leads to the vascular damage associated with diabetic retinopathy.

The research is published in the Jan. 29 issue of the .

"Our earlier research showed that high 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 in a Nature paper, so we decided to investigate them. We had no idea if the siah-1 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. 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."

Explore further: Identifying abnormal protein levels in diabetic retinopathy

Related Stories

Identifying abnormal protein levels in diabetic retinopathy

May 12, 2008

Researchers in Massachusetts are reporting an advance in bridging huge gaps in medical knowledge about the biochemical changes that occur inside the eyes of individuals with diabetic retinopathy (DR) — a leading cause of ...

Natural compound stops retinopathy

July 2, 2009

Researchers at the University of Oklahoma Health Sciences Center have found a way to use a natural compound to stop one of the leading causes of blindness in the United States. The research appears online this month in the ...

Blocking protein may prevent blinding disease

September 16, 2009

Blocking a protein that battles infection may help thwart a common cause of vision loss in chronic diseases such as diabetes, Medical College of Georgia researchers say.

Recommended for you

The universe's most miraculous molecule

October 9, 2015

It's the second most abundant substance in the universe. It dissolves more materials than any other solvent. It stores incredible amounts of energy. Life as we know it would not be possible without it. And although it covers ...

New method facilitates research on fuel cell catalysts

October 8, 2015

While the cleaning of car exhausts is among the best known applications of catalytic processes, it is only the tip of the iceberg. Practically the entire chemical industry relies on catalytic reactions. Therefore, catalyst ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.