增殖性玻璃體視網膜病變(Proliferative vitreoretinopathy, PVR)是病患在接受裂孔性視網膜剝離的手術後常見的後遺症之一，會導致嚴重的視覺受損甚至是失明。在PVR的致病機制中，視網膜色素表皮細胞會透過上皮-間質細胞轉換過程(Epithelium-mesenchymal transition, EMT)，從表皮細胞變成纖維母細胞樣細胞(Fibroblast-like cells)，隨後遷移、生長在玻璃體中形成視網膜上膜(Epiretinal membrane, ERM)並伴隨著細胞因子介白素(Interleukin)和基質金屬蛋白酶(matrix metalloproteinase)的蛋白含量上升。ERM會因為自身的收縮能力導致細胞收縮並拉扯視網膜，造成牽引性的視網膜剝離。目前臨床上對於PVR的治療方式主要是透過手術將ERM去除，但是手術的成功率卻不盡理想；到目前為止也沒有一個適合的藥物能夠來治療或是預防PVR的發生。因此，我們需要去尋找一個好的藥物及治療方法來解決目前臨床上遇到的困境。在本篇研究中，我們選擇了臨床上的一種抗生素，測試它是否能夠降低PVR的發生。我們在細胞實驗中發現到此抗生素可以降低人類視網膜色素表皮細胞(ARPE-19)的遷移、生長、收縮，也可以減少EMT過程中相關調控因子與酵素的活性。在動物實驗中，我們發現到此抗生素能夠在PVR小鼠模型中降低PVR和發炎指數，並且減緩小鼠中PVR的相關病徵。在PVR誘導的小鼠玻璃體或視網膜中，我們發現到與PVR相關的酵素、蛋白、細胞因子的含量會明顯上升，而抗生素的治療可以阻斷此機制。總結上述實驗結果，我們發現了一種藥物具有作為治療PVR的潛力。

Proliferative vitreoretinopathy (PVR) is a complication of surgery to correct rhegmatogenous retinal detachment and causes vision impairment and blindness in patients. During PVR development, retinal pigment epithelial (RPE) cells undergo epithelium-mesenchymal transition (EMT), migrate and proliferate in the vitreous, and form an epiretinal membrane with elevated levels of interleukin and matrix metalloproteinase (MMP). The membrane can attach to the retina and subsequently contract to cause retinal detachment and the failure of surgery. Until now, the major treatment for PVR is to remove the epiretinal membrane by surgery, but the success rate is unsatisfactory. The effective strategy to prevent PVR is also unavailable. Here, we test the potential of an antibiotic to treat PVR. In vitro results demonstrated that the antibiotic decreased the migration, proliferation, and contraction of the human RPE cell line, ARPE-19 and inhibited the activities of a regulator and enzyme, which are involved in the EMT process. In vivo results showed that antibiotic treatment decreased the disease score, inflammation, and pathology of PVR induced by ARPE-19 cells in mice. After PVR induction, enzyme expression can be positively regulated by a PVR associated pathway and cytokines, which were reversed by the antibiotic treatment, in the mouse retina and/or vitreous. Our results suggest that the antibiotic can be a new strategy to prevent PVR.

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