Minocycline Prevents the Formation of Acellular Capillaries in Mouse Models for Diabetic Retinopathy

Abstract

Listen

Translate article

Caspase-1 is responsible for the production of the pro-inflammatory cytokine interleukin-1β, which is known to induce vascular permeability, upregulation of adhesion molecules, and cell death among several other functions. We have previously shown that hyperglycemia induces the activation of caspase-1 in the retina of diabetic mice and humans. Therefore, this study is focused on the effect of minocycline, a second-generation tetracycline and proposed caspase-1 inhibitor, and inhibition of interleukin-1β signaling on retinal pathology in retinas of diabetic and galactose-fed mice. Mice made diabetic using streptozotocin or fed a galactose enriched diet were injected intraperitoneal with minocycline (5mg/kg body weight) 3 or 7 times a week for 2 months or 3 times a week for 6 months. At 2 months duration of diabetes, minocycline prevented hyperglycemia-induced activation of caspase-1 and subsequent interleukin-1β production in retinas of diabetic mice. Long-term studies revealed that minocycline significantly inhibited diabetes-induced formation of acellular capillaries in the retina of diabetic and galactosemic mice. In addition, interleukin-1β receptor knock-out mice we were protected from diabetes-induced retinal pathology at 7 months duration of diabetes. Therefore, the results indicate that activation of caspase-1 and subsequent production of interleukin-1β plays an important role in the development of diabetes-induced retinal pathology. Inhibition of this signaling pathway by using drugs such as minocycline might represent a potential new strategy to prevent the development of this disease.