A recent study funded by the National Institutes of Health (NIH) has shown a link between low blood sugar levels (hypoglycemia) and its worsening side effects on diabetic retinopathy which is a serious cause of vision loss in people with diabetes. This study, headed by specialists at the Wilmer Eye Institute at Johns Hopkins Medicine, demonstrates that hypoglycemia may impair the blood-retinal barrier, a key component that protects the eye's inner environment. (1)
Hidden Risk Behind Glucose Control
The new findings imply that strong glucose control may have an unanticipated risk, even if strict blood sugar control is a fundamental component of diabetic care. A protein known as the hypoxia-inducible factor (HIF) was shown to be enhanced in the diabetic mice during hypoglycemia, or periods of low blood sugar. Additionally, to control body's reaction to low oxygen levels, this protein has also been linked to abnormal blood vessel development and leakage within the retina.
In a diabetic mice, HIF accumulation has triggered the production of several vasoactive substances which are molecules that can increase blood vessel permeability. This led to the breakdown of the inner blood-retinal barrier (iBRB), allowing the fluid and proteins to leak into the retinal tissue. Such leakage can destroy the retina’s delicate neurovascular structure which ultimately leading to vision impairment or loss.
It's also fascinating to note that similar effects did not occur in animals those without diabetes, suggesting that diabetes makes people more susceptible to retinal injury due to hypoglycemia.
A Potential Breakthrough
Researchers examined an investigational medication called 32-134D, which suppresses both HIF-1α and HIF-2α, these being the two essential components of the HIF protein, to see if it may stop this chain reaction. The medication successfully decreased HIF levels and acquired the production of harmful vasoactive genes in diabetic mice before provoking hypoglycemic episodes. Vascular leakage was thus greatly decreased, while the iBRB was left intact. (2)
These encouraging findings suggest that 32-134D may be used as a therapeutic agent to slow the course of diabetic retinopathy, especially in individuals who are just starting aggressive therapy for reducing glucose levels or who are frequently experiencing blood sugar swings.
Implications for Diabetes Care
According to Dr. Akrit Sodhi, lead author and ophthalmology professor at Johns Hopkins, the study may help explain why some patients experience a paradoxical worsening of eye disease after initiating tight glucose control. The findings promote the idea that, while avoiding high blood sugar is vital, avoiding frequent or severe lows may be just as important for long-term eye health. (3)
Therapies targeting the HIF pathway could offer a new avenue to protect vision in diabetic patients, especially those at high risk of retinopathy progression.Dr. Akrit Sodhi, Ophthalmology Professor, Johns Hopkins
Dr. Akrit Sodhi said the discovery could help explain why some patients have a paradoxical worsening of their eye illness after starting strict glucose management.
The findings suggest that preventing frequent or extremely low blood sugar levels may be as important for long-term eye health as reducing high blood sugar levels.
"Treatments that target the HIF pathway may provide a new way to protect vision in diabetic patients, particularly those who are at high risk of developing retinopathy,"Dr. Akrit Sodhi, Ophthalmology Professor, Johns Hopkins
So, What’s Next?
The study team hopes to move 32-134D into human therapeutic trials and intends to keep investigating the role of HIF in retinal disorders. If effective, this medication might mark a significant change in the way diabetic eye illness is treated, going beyond blood sugar regulation to directly shield the retina from molecular harm.
Although diabetic retinopathy continues to be a major preventable cause of blindness globally, these discoveries pave the way for novel approaches that seek to protect vision and enhance the lives of millions of diabetics.
References:
News-Medical.net. "Low Blood Sugar Linked to Retinal Damage in Diabetic Eye Disease." News-Medical.net, May 6, 2025. https://www.news-medical.net/news/20250506/Low-blood-sugar-linked-to-retinal-damage-in-diabetic-eye-disease.aspx.
Sodhi, Akrit, et al. "Hypoglycemia Promotes Inner Blood-Retinal Barrier Breakdown and Retinal Vascular Leakage via Hypoxia-Inducible Factor Activation." Science Translational Medicine, vol. 17, no. 689, 2025, eadq5355. https://doi.org/10.1126/scitranslmed.adq5355.
Neuroscience News. "Low Blood Sugar Triggers Retinal Damage, Vision Loss." Neuroscience News, May 7, 2025. https://neurosciencenews.com/low-blood-vision-retina-28836/.
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