Use of Myriocin as co-adjuvant in glaucoma surgery: An in vitro study

Abstract

Mitomycin C as well as other antiproliferative drugs are off-label agents widely used to prevent the failure of glaucoma surgery due to activation of Tenon’s fibroblasts and the ensuing excessive subconjunctival scarring. Though efficacious, these treatments are associated with some severe long-term complications, so it is crucial to investigate less cytotoxic compounds as adjuvant therapy in glaucoma surgery. The aim of this study was to evaluate the effect and potential cytotoxicity of Myriocin, a natural sphingolipid synthesis inhibitor, on TGF-β1-induced myofibroblasts transformation of human dermal fibroblasts. We found that myriocin significantly attenuated the transcript levels of αSMA, CTGF, and MMP9 which are involved in the fibrosis process. Mitomycin C poorly affects the same pro-fibrotic markers while reducing fibroblasts motility as much as myriocin. At similar doses, five minutes of mitomycin C treatment consistently affects human dermal fibroblast viability and proliferation compared to prolonged myriocin application, strengthening already published data on the good tolerability of this natural compound. Our results draw attention to the use of myriocin as an adjuvant in glaucoma surgery due to the effectiveness in reducing fibroblasts to myofibroblasts transformation and the low cytotoxicity.