Department of Cell Biology, UCL Institute of Ophthalmology, London, United Kingdom.
Invest Ophthalmol Vis Sci. 2013 Jul 12;54(7):4675-82. doi: 10.1167/iovs.13-11787.
Trachoma is a conjunctival scarring disease, which is the leading infectious cause of blindness worldwide. Elimination of blinding trachoma is being held back by the high rate of trichiasis recurrence following surgery. There is currently no treatment available to suppress the profibrotic state and reduce recurrence. Although the mechanisms underlying trichiasis development are unknown, the profibrotic phenotype has been linked to matrix metalloproteinase (MMP) expression. Doxycycline, a well-known tetracycline antibiotic, can act as a broad MMP inhibitor and has showed some success in preventing fibrosis in various clinical contexts. The purpose of this work was to assess the antiscarring properties of doxycycline in an in vitro model of trichiasis fibroblast-mediated tissue contraction.
Primary cultures of fibroblasts were established from conjunctival samples obtained from normal donors or during surgery for trachomatous trichiasis. The effect of doxycycline on matrix contraction was investigated in our standard collagen gel contraction model. Cell morphology and matrix integrity were assessed using confocal reflection microscopy. Quantitative real time polymerase chain reaction and a FRET-based assay were used to measure MMP expression and activity, respectively.
Doxycycline treatment successfully suppressed the contractile phenotype of trichiasis fibroblasts, matrix degradation, and significantly altered the expression of MMP1, MMP9, and MMP12 associated with the profibrotic phenotype.
In view of the results presented here and the wider use of doxycycline in clinical settings, we propose that doxycycline might be useful as a treatment to prevent recurrence following trichiasis surgery.
沙眼是一种结膜瘢痕疾病，是全球致盲的主要传染性病因。手术后，由于睫毛乱生的复发率高，阻碍了致盲性沙眼的消除。目前尚无抑制纤维增生状态和减少复发的治疗方法。尽管睫毛乱生的发展机制尚不清楚，但纤维增生表型与基质金属蛋白酶（MMP）表达有关。强力霉素，一种众所周知的四环素抗生素，可作为一种广泛的 MMP 抑制剂，并已在各种临床情况下预防纤维化方面取得了一定的成功。本研究旨在评估强力霉素在睫毛乱生纤维母细胞介导的组织收缩体外模型中的抗瘢痕形成特性。
从正常供体或沙眼性睫毛乱生手术中获得的结膜样本中建立原代纤维母细胞培养物。在我们的标准胶原凝胶收缩模型中研究强力霉素对基质收缩的影响。使用共聚焦反射显微镜评估细胞形态和基质完整性。定量实时聚合酶链反应和基于 FRET 的测定分别用于测量 MMP 表达和活性。
强力霉素治疗成功抑制了睫毛乱生纤维母细胞的收缩表型、基质降解，并显著改变了与纤维增生表型相关的 MMP1、MMP9 和 MMP12 的表达。
鉴于这里提出的结果以及强力霉素在临床环境中的更广泛应用，我们建议强力霉素可能是一种有用的治疗方法，可预防睫毛乱生手术后的复发。
