Low blood sugar, also called hypoglycemia, may do more than make you feel shaky or tired—it could damage your eyes.
A new study funded by the National Institutes of Health and led by researchers at the Wilmer Eye Institute at Johns Hopkins Medicine has found that hypoglycemia may cause the breakdown of the blood-retinal barrier, a protective layer that controls the movement of nutrients, waste, and water in and out of the retina. This barrier is vital for healthy vision.
The findings, published in Science Translational Medicine, help explain one way diabetic retinopathy can develop or get worse. Diabetic retinopathy is a serious complication of both type 1 and type 2 diabetes that can lead to permanent vision loss if not treated.
The researchers focused on a protein called hypoxia-inducible factor (HIF), which has been linked before to diabetic retinopathy and other eye diseases. In this new work, they discovered that during low blood sugar episodes, HIF builds up in certain retinal cells.
This protein can trigger the production of other proteins that lead to excessive growth and leakage in the tiny blood vessels of the retina.
To study this, scientists used diabetic and non-diabetic mice. They induced episodes of hypoglycemia in both groups.
The diabetic mice showed a sharp rise in HIF levels during low blood sugar, which was enough to weaken and damage the blood-retinal barrier, leading to leaky retinal blood vessels. Non-diabetic mice did not experience the same rise in HIF and did not have the same damage.
The team then tested an experimental drug called 32-134D, which blocks HIF. Diabetic mice that received 32-134D before low blood sugar episodes had lower HIF levels. This prevented the chain reaction that normally leads to barrier breakdown and blood vessel leakage.
According to senior author Dr. Akrit Sodhi, these results may explain why some people with diabetes—especially those who start strict glucose control or have big swings in blood sugar—sometimes see their eye disease worsen at first. It also points to HIF as a promising target for new treatments.
The researchers now plan to continue studying how HIF affects the blood-retinal barrier and to test 32-134D further, with the hope of eventually running clinical trials in people with diabetic retinopathy.
This work offers new hope for preventing or slowing one of the most common causes of blindness in people with diabetes, and highlights the importance of avoiding frequent or severe low blood sugar episodes.
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The study is published in Science Translational Medicine.
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