Diabetic retinopathy is the leading cause of blindness among working-age adults in the United States and one of the top causes of vision loss worldwide. It affects people with both type 1 and type 2 diabetes. Current treatments are invasive and offer limited protection.
Controlling blood sugar through diet, exercise, and medication helps prevent or slow the progression of diabetic retinopathy. However, many patients experience a worsening of their eye condition during the first 12 to 18 months after starting treatment.
Experts believe this happens because the retina is “shocked” when blood sugar drops quickly due to insulin therapy. Lars Michael Larsen, an ophthalmologist at the University of Copenhagen, called this a long-standing paradox. While the retinopathy usually stabilizes after about a year, the initial damage can be serious.
New findings from Akrit Sodhi and his team at Johns Hopkins University School of Medicine shed light on this problem. Their research shows that low blood sugar, known as hypoglycemia, worsens damage to the small blood vessels in the retina by changing how certain genes work in retinal cells. In mouse studies, an experimental drug was able to block these harmful gene changes and protect the retina. This offers a possible way to solve the treatment paradox.
Diabetic retinopathy occurs when blood vessels in the back of the eye break down. These damaged vessels leak blood and fluid, causing inflammation and abnormal blood vessel growth, which can lead to vision loss over time.
“Diabetic retinopathy is almost expected in patients with diabetes,” Sodhi said. “If it is allowed to progress, it will eventually cause vision loss.”
In earlier research, Sodhi’s team found that short periods of low blood sugar increase the production of a protein called hypoxia inducible factor (HIF). HIF controls many genes, including those that regulate blood vessel growth. In their new study, they compared how high levels of HIF affected diabetic and non-diabetic mice.
Non-diabetic mice tolerated the increased HIF well. But diabetic mice developed blood vessel leakage in the retina, a sign of damage, after only three months of diabetes. The experimental drug 32-134D, which blocks HIF, prevented this damage.
Current standard treatments for diabetic retinopathy use drugs that inhibit vascular endothelial growth factor (VEGF), a protein controlled by HIF. Blocking HIF not only reduced VEGF activity but also lowered other genes related to blood vessel growth in diabetic mice. Since HIF controls hundreds of genes, researchers will carefully watch for possible side effects in future studies.
“We are preparing to test this drug in patients,” Sodhi said. “There is potential benefit, but we also need to monitor for risks linked to blocking HIF.”
Larsen, who was not part of the new study, said the results are promising. He emphasized that in clinical practice, it is important to focus on stable blood sugar levels, not just lowering them quickly.
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