Published March 26, 2013
Sarah X. Zhang, MD, is using a $1.1 million grant to study a possible mechanism underlying diabetic retinopathy and test a novel protective agent to thwart it.
This research could lead to new therapies to treat or prevent this prevalent condition as well as other sight-threatening diseases—such as age-related macular degeneration—that may involve the same mechanism.
The National Eye Institute is funding Zhang’s current study with a five-year, $1.8 million grant awarded in 2010.
Zhang’s research team is exploring how endoplasmic reticulum stress and the resulting unfolded protein response contribute to the regulation of vascular function and the development of diabetic complications.
“We hypothesize that diabetes-induced endoplasmic reticulum stress promotes inflammation and is thereby a driving force … leading to diabetic retinopathy,” says Zhang, an associate professor of ophthalmology who joined the School of Medicine and Biomedical Sciences in 2012.
The researchers also are testing the therapeutic potential of X-box binding protein 1 (XBP-1), an endogenous inhibitor of endoplasmic reticulum stress.
A recent study by Zhang’s group suggests that exposing mouse retinas to mild stress could activate the unfolded protein response and protect the retina against harmful inflammatory processes.
During the early stage of diabetes, retinal cells are imposed with mild, temporary stress, which can be overcome by this intricate set of signaling pathways.
With disease progression, however, cumulative stress reaches a certain threshold, and the protective signaling fails to alleviate the stress, activating detrimental molecular pathways. These harmful pathways could lead to chronic retinal inflammation.
Zhang’s studies use state-of-the-art genetic modification techniques and various biochemical approaches to decipher mechanisms of neuronal degeneration and aberrant angiogenesis of the retina at molecular levels.
Genetically engineered mice will help the researchers determine if XBP-1 can successfully block the onset or progression of diabetic retinopathy.
Diabetic retinopathy is the most frequent cause of blindness in the working-age population in developed countries. Each year, 12,000 to 24,000 Americans with diabetes become blind, notes Zhang.
An estimated 40 percent of diabetic Americans over age 40 have some form of retinopathy.
According to the American Diabetes Association, 25.8 million Americans—8.3 percent of the U.S. population—have diabetes, and 1.9 million new cases were diagnosed in 2010 in those 20 and older.