Sacchi Matteo, Tomaselli Davide, Ruggeri Maria Ludovica, Aiello Francesca Bianca, Sabella Pierfilippo, Dore Stefano, Pinna Antonio, Mastropasqua Rodolfo, Nubile Mario, Agnifili Luca
Ophthalmology Unit, Azienda Ospedaliero-Universitaria di Sassari, 07100 Sassari, Italy.
Ophthalmology Clinic, Alessandro Manzoni Hospital, ASST Lecco, 23900 Lecco, Italy.
Int J Mol Sci. 2025 Mar 5;26(5):2327. doi: 10.3390/ijms26052327.
Filtration bleb (FB) fibrosis represents the primary risk factor for glaucoma filtration surgery (GFS) failure. We reviewed the most recent literature on post-GFS fibrosis in humans, focusing on novel molecular pathways and antifibrotic treatments. Three main literature searches were conducted. First, we performed a narrative review of two models of extra-ocular fibrosis, idiopathic pulmonary fibrosis and skin fibrosis, to improve the comprehension of ocular fibrosis. Second, we conducted a systematic review of failed FB features in the PubMed, Embase, and Cochrane Library databases. Selected studies were screened based on the functional state and morphological features of FB. Third, we carried out a narrative review of novel potential antifibrotic molecules. In the systematic review, 11 studies met the criteria for analysis. Immunohistochemistry and genomics deemed SPARC and transglutaminases to be important for tissue remodeling and attributed pivotal roles to TGFβ and M2c macrophages in promoting FB fibrosis. Four major mechanisms were identified in the FB failure process: inflammation, fibroblast proliferation and myofibroblast conversion, vascularization, and tissue remodeling. On this basis, an updated model of FB fibrosis was described. Among the pharmacological options, particular attention was given to nintedanib, pirfenidone, and rapamycin, which are used in skin and pulmonary fibrosis, since their promising effects are demonstrated in experimental models of FB fibrosis. Based on the most recent literature, modern patho-physiological models of FB fibrosis should consider TGFβ and M2c macrophages as pivotal players and favorite targets for therapy, while research on antifibrotic strategies should clinically investigate medications utilized in the management of extra-ocular fibrosis.
滤过泡（FB）纤维化是青光眼滤过手术（GFS）失败的主要危险因素。我们回顾了关于人类GFS术后纤维化的最新文献，重点关注新的分子途径和抗纤维化治疗。进行了三项主要文献检索。首先，我们对两种眼外纤维化模型，即特发性肺纤维化和皮肤纤维化进行了叙述性综述，以增进对眼部纤维化的理解。其次，我们在PubMed、Embase和Cochrane图书馆数据库中对失败的FB特征进行了系统综述。根据FB的功能状态和形态特征筛选选定的研究。第三，我们对新的潜在抗纤维化分子进行了叙述性综述。在系统综述中，有11项研究符合分析标准。免疫组织化学和基因组学认为，富含半胱氨酸的酸性分泌蛋白（SPARC）和转谷氨酰胺酶对组织重塑很重要，并认为转化生长因子β（TGFβ）和M2c巨噬细胞在促进FB纤维化中起关键作用。在FB失败过程中确定了四个主要机制：炎症、成纤维细胞增殖和肌成纤维细胞转化、血管生成和组织重塑。在此基础上，描述了一个更新的FB纤维化模型。在药理学选择中，特别关注了用于皮肤和肺纤维化的尼达尼布、吡非尼酮和雷帕霉素，因为它们在FB纤维化实验模型中显示出有前景的效果。根据最新文献，FB纤维化的现代病理生理模型应将TGFβ和M2c巨噬细胞视为关键参与者和治疗的理想靶点，而抗纤维化策略的研究应在临床上研究用于治疗眼外纤维化的药物。
