Tight glycaemic control (TGC) is known to reduce the risk and/or progression of diabetic retinopathy, a diabetes mellitus complication that causes the breakdown of the inner blood–retinal barrier (iBRB), leading to vision loss. However, intensive TGC in the early stages of diabetic retinopathy can lead to a worsening of the condition. Building on the authors’ previous work, a study in Science Translational Medicine explores the mechanisms behind this apparent paradox and potential therapeutic avenues for reducing TGC-associated diabetic retinopathy.

“Hypoglycaemia results in the early but transient accumulation of HIF1α and the late but sustained accumulation of HIF2α in inner retinal cells,” says corresponding author Akrit Sodhi. “This, in turn, results in the expression of dozens of HIF-dependent vasoactive mediators.” Increased expression of these factors owing to transient hypoglycaemia was not sufficient to induce iBRB breakdown in the retinas of healthy mice, but did cause vascular leakage in the retinas of mice with streptozotocin-induced diabetes mellitus.