JCI - Targeting hypoxia-inducible factors with 32-134D safely and effectively treats diabetic eye disease in mice

Many patients with diabetic eye disease respond inadequately to anti-VEGF therapies, implicating additional vasoactive mediators in its pathogenesis. We demonstrate that levels of angiogenic proteins regulated by hypoxia-inducible factor -1 and -2 remain elevated in diabetic eyes despite treatment with anti-VEGF therapy. Conversely, by inhibiting HIFs we normalized the expression of multiple vasoactive mediators in mouse models of diabetic eye disease.

However, while the HIF-inhibitor acriflavine prevented retinal vascular hyperpermeability in diabetic mice for several months following a single intraocular injection, accumulation of acriflavine in the retina resulted in retinal toxicity over time, raising concerns for its use in patients.

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