Glaucoma, the second leading cause of blindness worldwide, is characterized by aberrant elevations of intraocular pressure (IOP), which can damage the optic nerve. IOP reduction is the only effective therapy for prevention of visual impairment and blindness in both hypertensive and normotensive individuals, and in some cases, trabeculectomy is a major surgical procedure that can lower IOP in patients with glaucoma. No matter how surgical technique and postoperative care advances, excessive scarring and tissue fibrosis could result from increased human conjunctival fibroblast (HCF) proliferation and extracellular matrix (ECM) deposition of the subconjunctival tissue and scleral flaps would persist after trabeculectomy. And these issues are major impediments to IOP reduction and filtering of bleb formations, so the modulation of the factors which can induce fibrosis could used as a novel strategy to control scarring after trabeculectomy. In this study, we examined the effects of mammalian target of rapamycin (mTOR) inhibitors (rapamycin or Torin1) on the fibrotic response induced by transforming growth factor-beta 1 (TGF-β1) in cultured human conjunctival fibroblast (HCF) cells. The study also examined the effects of mTOR inhibitor on fibrosis after trabeculectomy in rabbit eyes. In in vitro studies, we stimulated HCFs with TGF-β1, and confirmed that the expression levels of fibronectin, collagen type I alpha 1 chain (COL1A1), and α-smooth muscle actin (SMA) were significantly upregulated in HCFs with TGF-β1, by means of quantitative real-time polymerase chain reaction and immunocytochemistry. And those TGF-β1-induced changes were significantly attenuated with mTOR inhibitors, rapamycin or Torin1. Additionally the migration rate of HCFs was examined under conditions of TGF-β1 induction, TGF-β1-induced changes were significantly attenuated with mTOR inhibitors. A rabbit model of trabeculectomy was examined in vivo, and the effects of topical mTOR inhibitor were also examined, and found that topical treatment with mTOR inhibitor significantly suppressed collagen deposition in rabbit eyes after trabeculectomy. These results have demonstrated that mTOR inhibitors may provide a novel treatment modality for reducing the fibrotic response in HCFs and improving bleb scarring after filtration surgery.

青光眼是全球第二大失明的主要原因，其特征在于眼内压（IOP）异常升高，会损害视神经。在高血压和血压正常的人中，降低IOP是预防视力障碍和失明的唯一有效疗法，在某些情况下，小梁切除术是一种可以降低青光眼患者IOP的主要手术方法。无论外科手术技术和术后护理如何发展，人结膜成纤维细胞（HCF）增殖增加都可能导致过多的疤痕和组织纤维化，小梁切除术后结膜下组织和巩膜瓣的细胞外基质沉积仍将持续。这些问题是减少IOP和过滤气泡形成的主要障碍，因此调节引起纤维化的因素可作为控制小梁切除术后瘢痕形成的一种新策略。在这项研究中，我们检查了哺乳动物雷帕霉素（mTOR）抑制剂（雷帕霉素或Torin1）对培养的人结膜成纤维细胞（HCF）细胞中转化生长因子-β1（TGF-β1）诱导的纤维化反应的影响。该研究还检查了mTOR抑制剂对兔眼小梁切除术后纤维化的作用。在 该研究还检查了mTOR抑制剂对兔眼小梁切除术后纤维化的作用。在 该研究还检查了mTOR抑制剂对兔眼小梁切除术后纤维化的作用。在在体外研究中，我们用TGF-β1刺激了HCF，并证实在TGF-β1的HCF中，纤连蛋白，I型胶原1型胶原（COL1A1）和α-平滑肌肌动蛋白（SMA）的表达水平显着上调，通过实时定量聚合酶链反应和免疫细胞化学。并用mTOR抑制剂雷帕霉素或Torin1显着减弱了TGF-β1诱导的变化。另外，在TGF-β1诱导的条件下检查HCF的迁移速率，用mTOR抑制剂显着减弱了TGF-β1诱导的变化。在体内检查了小梁切除术的兔子模型，还检查了局部mTOR抑制剂的作用，发现用mTOR抑制剂进行局部治疗可显着抑制小梁切除术后兔眼中的胶原沉积。这些结果表明，mTOR抑制剂可提供一种新颖的治疗方式，以减少HCF中的纤维化反应并改善滤过术后的瘢痕形成。