A new NIH-funded study from Johns Hopkins’ Wilmer Eye Institute suggests that low blood sugar may damage the blood-retinal barrier, which regulates essential exchanges in the retina. Researchers observed this effect in diabetic mice, offering new insight into how hypoglycemia may contribute to diabetic retinopathy. This condition, common in both type 1 and type 2 diabetes, can lead to irreversible vision loss if untreated. The study found that during hypoglycemic episodes, a protein called hypoxia-inducible factor (HIF) builds up in retinal cells. These findings were published on April 30 in Science Translational Medicine.
HIF, a protein previously linked to diabetic retinopathy, can trigger excess production of proteins that cause blood vessel overgrowth and leakage in the retina. Researchers found that HIF also contributes to the breakdown of the blood-retinal barrier during hypoglycemia. When low blood sugar was induced in mice, only those with diabetes showed elevated HIF levels, leading to retinal vessel leakage. This barrier breakdown plays a key role in the retinal damage and vision loss seen in diabetic retinopathy.
The team investigated further by testing an experimental drug known as 32-134D, which inhibits the HIF protein. Some diabetic mice received an injection of 32-134D prior to induced episodes of low blood sugar, and researchers observed lower HIF levels, in turn preventing the expression of proteins that promote the breakdown of the blood-retinal barrier and blood vessel leakage.
“These studies help explain why patients with diabetes who are initially started on tight glucose control, the cornerstone of diabetic management, or those who have high glycemic variability (transient episodes of very low — followed by very high — serum glucose levels), experience worsening of their diabetic eye disease,” says corresponding author Akrit Sodhi, M.D., Ph.D., associate professor of ophthalmology and the Branna and Irving Sisenwein Professor of Ophthalmology at the Johns Hopkins University School of Medicine and the Wilmer Eye Institute. “Our findings underscore why therapies targeting HIF will be an effective approach to prevent or treat diabetic retinopathy.”
Researchers are planning future studies on HIF, the breakdown of the blood-retinal barrier and 32-134D, and hope to conduct clinical studies of 32-134D in patients with diabetic retinopathy.
Read the full news release from Johns Hopkins Medicine.
Source: Johns Hopkins Medicine