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Corneal fibrosis: From in vitro models to current and upcoming drug and gene medicines
Advanced Drug Delivery Reviews ( IF 15.2 ) Pub Date : 2024-04-19 , DOI: 10.1016/j.addr.2024.115317 Laura Trujillo Cubillo 1 , Mehmet Gurdal 1 , Dimitrios I Zeugolis 1
Advanced Drug Delivery Reviews ( IF 15.2 ) Pub Date : 2024-04-19 , DOI: 10.1016/j.addr.2024.115317 Laura Trujillo Cubillo 1 , Mehmet Gurdal 1 , Dimitrios I Zeugolis 1
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Fibrotic diseases are characterised by myofibroblast differentiation, uncontrolled pathological extracellular matrix accumulation, tissue contraction, scar formation and, ultimately tissue / organ dysfunction. The cornea, the transparent tissue located on the anterior chamber of the eye, is extremely susceptible to fibrotic diseases, which cause loss of corneal transparency and are often associated with blindness. Although topical corticosteroids and antimetabolites are extensively used in the management of corneal fibrosis, they are associated with glaucoma, cataract formation, corneoscleral melting and infection, imposing the need of far more effective therapies. Herein, we summarise and discuss shortfalls and recent advances in models (e.g. transforming growth factor-β (TGF-β) / ascorbic acid / interleukin (IL) induced) and drug (e.g. TGF-β inhibitors, epigenetic modulators) and gene (e.g. gene editing, gene silencing) therapeutic strategies in the corneal fibrosis context. Emerging therapeutical agents (e.g. neutralising antibodies, ligand traps, receptor kinase inhibitors, antisense oligonucleotides) that have shown promise in clinical setting but have not yet assessed in corneal fibrosis context are also discussed.
中文翻译：
角膜纤维化：从体外模型到当前和即将推出的药物和基因药物
纤维化疾病的特征是肌成纤维细胞分化、不受控制的病理性细胞外基质积累、组织收缩、疤痕形成以及最终的组织/器官功能障碍。角膜是位于眼睛前房的透明组织，极易受到纤维化疾病的影响，从而导致角膜透明度丧失，并常常导致失明。尽管局部皮质类固醇和抗代谢药物广泛用于治疗角膜纤维化，但它们与青光眼、白内障形成、角巩膜溶解和感染有关，因此需要更有效的治疗方法。在此，我们总结并讨论了模型（例如转化生长因子-β（TGF-β）/抗坏血酸/白细胞介素（IL）诱导）、药物（例如TGF-β抑制剂、表观遗传调节剂）和基因（例如基因编辑、基因沉默）在角膜纤维化背景下的治疗策略。还讨论了在临床环境中显示出前景但尚未在角膜纤维化背景下进行评估的新兴治疗剂（例如中和抗体、配体陷阱、受体激酶抑制剂、反义寡核苷酸）。
更新日期：2024-04-19
中文翻译：
角膜纤维化：从体外模型到当前和即将推出的药物和基因药物
纤维化疾病的特征是肌成纤维细胞分化、不受控制的病理性细胞外基质积累、组织收缩、疤痕形成以及最终的组织/器官功能障碍。角膜是位于眼睛前房的透明组织，极易受到纤维化疾病的影响，从而导致角膜透明度丧失，并常常导致失明。尽管局部皮质类固醇和抗代谢药物广泛用于治疗角膜纤维化，但它们与青光眼、白内障形成、角巩膜溶解和感染有关，因此需要更有效的治疗方法。在此，我们总结并讨论了模型（例如转化生长因子-β（TGF-β）/抗坏血酸/白细胞介素（IL）诱导）、药物（例如TGF-β抑制剂、表观遗传调节剂）和基因（例如基因编辑、基因沉默）在角膜纤维化背景下的治疗策略。还讨论了在临床环境中显示出前景但尚未在角膜纤维化背景下进行评估的新兴治疗剂（例如中和抗体、配体陷阱、受体激酶抑制剂、反义寡核苷酸）。
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