EMMPRIN aggravates angiogenesis and blood-retina barrier injury by regulating matrix metalloproteinases in diabetic retinopathy

<b>Background:</b> Diabetic retinopathy (DR) is a microangiopathy resulting from diabetes mellitus. Studies on vitreous samples have shed insights into the etiology of DR and highlighted the role of molecular targets in DR treatment. The present study probed into the role of extracellular matrix metalloproteinase inducer (EMMPRIN) in DR by examining its influence on inflammation, angiogenesis, matrix metalloproteinases (MMPs), and blood-retina barrier injury.<b>Methods:</b> After the induction of diabetes in rats through streptozotocin injection, SP-8356 (an inhibitor for EMMPRIN) was administered to rats for silencing EMMPRIN <i>in vivo</i>. Serum and vitreous EMMPRIN levels were assessed by ELISA and western blotting. The concentration and mRNA expression of proinflammatory cytokines in rat vitreous samples were quantified through ELISA or RT-qPCR. Western blotting or RT-qPCR was performed to measure protein or mRNA levels of MMPs, tight junction factors, and angiogenic factors.<b>Results:</b> High EMMPRIN levels were found in both serum and vitreous samples of DR rats. Inhibition of EMMPRIN using SP-8356 ameliorated DR-induced high levels of inflammatory cytokines, MMPs, and angiogenic factors and rescued DR-induced low expression levels of tight junction factors in rat vitreous samples.<b>Conclusions:</b> EMMPRIN accelerates inflammation, angiogenesis and blood-retina barrier injury in DR by regulating MMPs.