Activation of Tenon's capsule fibroblasts limits the success rate of glaucoma filtration surgery (GFS), the most efficacious therapy for patients with glaucoma. Angiotensin type 1 receptor (AGTR1) is involved in tissues remodeling and fibrogenesis. However, whether AGTR1 is involved in the progress of fibrogenesis after GFS is not fully elucidated. The aim of this study was to investigate the role of an AGTR1 in scar formation after GFS and the potential anti-fibrosis effect of AGTR1 blocker. AGTR1 expression level was increased in subconjunctival tissues in a rat model of GFS and transforming growth factor-beta 2 (TGF-β2)-induced human Tenon's capsule fibroblasts (HTFs). AGTR1 blocker treatment suppressed TGF-β2-induced HTF migration and α-smooth muscle actin (α-SMA) and fibronectin (FN) expression. AGTR1 blocker treatment also attenuated collagen deposition and α-SMA and FN expression in subconjunctival tissues of the rat model after GFS. Moreover, AGTR1 blocker decreased TGF-β2-induced P65 phosphorylation, P65 nuclear translocation, and nuclear factor kappa B (NF-κB) luciferase activity. Additionally, BAY 11–7082 (an NF-κB inhibitor) significantly suppressed HTF fibrosis. In conclusion, our results indicate that AGTR1 is involved in scar formation after GFS. The AGTR1 blocker attenuates subconjunctival fibrosis after GFS by inhibiting the NF-κB signaling pathway. These findings indicate that targeting AGTR1 is a potential approach to attenuate fibrosis after GFS.

Tenon 囊成纤维细胞的激活限制了青光眼滤过手术 (GFS) 的成功率，而青光眼滤过手术是青光眼患者最有效的治疗方法。 1 型血管紧张素受体 (AGTR1) 参与组织重塑和纤维生成。然而，AGTR1是否参与GFS后纤维发生的进展尚未完全阐明。本研究的目的是探讨 AGTR1 在 GFS 后疤痕形成中的作用以及 AGTR1 阻滞剂的潜在抗纤维化作用。在 GFS 和转化生长因子-β 2 (TGF-β2) 诱导的人 Tenon 囊成纤维细胞 (HTF) 大鼠模型中，AGTR1 表达水平在大鼠结膜下组织中增加。 AGTR1 阻断剂治疗抑制 TGF-β2 诱导的 HTF 迁移以及 α-平滑肌肌动蛋白 (α-SMA) 和纤连蛋白 (FN) 的表达。 AGTR1 阻断剂治疗还减弱了 GFS 后大鼠模型结膜下组织中的胶原蛋白沉积以及 α-SMA 和 FN 表达。此外，AGTR1 阻断剂可降低 TGF-β2 诱导的 P65 磷酸化、P65 核转位和核因子 kappa B (NF-κB) 荧光素酶活性。此外，BAY 11–7082（一种 NF-κB 抑制剂）可显着抑制 HTF 纤维化。总之，我们的结果表明 AGTR1 参与 GFS 后疤痕的形成。 AGTR1 阻滞剂通过抑制 NF-κB 信号通路来减轻 GFS 后的结膜下纤维化。这些发现表明，靶向 AGTR1 是减轻 GFS 后纤维化的潜在方法。