Low Intraocular Pressure Induces Fibrotic Changes in the Trabecular Meshwork and Schlemm's Canal of Sprague Dawley Rats.

IF 2.6 3区医学 Q2 OPHTHALMOLOGY Translational Vision Science & Technology Pub Date : 2024-10-01 DOI:10.1167/tvst.13.10.10

Lijuan Xu, Yin Zhao, Xinyao Zhang, Xiaorui Gang, Jialing Han, Tao Zhou, Binyan Qi, Shuning Song, Ruiyi Ren, Yuanbo Liang

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Abstract

Purpose: Continuous artificial aqueous humor drainage in the eyes of patients with glaucoma undergoing trabeculectomy likely exerts abnormal shear stress. However, it remains unknown how changes in intraocular pressure (IOP) can affect aqueous humor outflow (AHO).

Methods: Here, we induced and maintained low intraocular pressure (L-IOP) in healthy Sprague Dawley (SD) rats by puncturing their eyes using a tube (200-µm diameter) for 2 weeks. After the rats were euthanized, their eyes were removed, fixed, embedded, stained, and scanned to analyze the physiological and pathological changes in the trabecular meshwork (TM) and Schlemm's canal (SC). We measured SC parameters using ImageJ software and assessed the expression of various markers related to flow shear stress (KLF4), fibrosis (TGF-β1, TGF-β2, α-SMA, pSmad1/5, pSmad2/3, and fibronectin), cytoskeleton (integrin β1 and F-actin), diastolic function (nitric oxide synthase and endothelial nitric oxide synthase [eNOS]), apoptosis (cleaved caspase-3), and proliferation (Ki-67) using immunofluorescence or immunohistochemistry.

Results: L-IOP eyes showed a larger SC area, higher eNOS expression, and lower KLF4 and F-actin expression in the TM and SC (both P < 0.05) than control eyes. The aqueous humor of L-IOP eyes had a higher abundance of fibrotic proteins and apoptotic cells than that of control eyes, with significantly higher TGF-β1, α-SMA, fibronectin, and cleaved caspase-3 expression (all P < 0.05).

Conclusions: In conclusion, a persistence of L-IOP for 2 weeks may contribute to fibrosis in the TM and SC and might be detrimental to conventional AHO in SD rat eyes.

Translational relevance: Clinicians should consider that aberrant shear force induced by aqueous humor fluctuation may damage AHO outflow channel when treating patients.

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低眼压诱导 Sprague Dawley 大鼠小梁网和施莱姆管发生纤维化变化

目的：在接受小梁切除术的青光眼患者眼中，持续的人工房水引流可能会产生异常剪切应力。方法：在此，我们用一根直径为 200 微米的管子穿刺健康的 Sprague Dawley（SD）大鼠的眼睛，诱导并维持低眼压（L-IOP）2 周。大鼠安乐死后，取出眼球并固定、包埋、染色和扫描，以分析小梁网（TM）和Schlemm管（SC）的生理和病理变化。我们使用 ImageJ 软件测量了 SC 参数，并评估了与血流剪切应力（KLF4）、纤维化（TGF-β1、TGF-β2、α-SMA、pSmad1/5、pSmad2/3 和纤维连接蛋白）相关的各种标记物的表达、使用免疫荧光或免疫组织化学方法检测细胞骨架（整合素β1和F-肌动蛋白）、舒张功能（一氧化氮合酶和内皮一氧化氮合酶[eNOS]）、细胞凋亡（裂解的caspase-3）和增殖（Ki-67）。结果显示与对照组相比，低视力患者眼球的 SC 面积更大，eNOS 表达更高，TM 和 SC 中的 KLF4 和 F-actin 表达更低（P 均<0.05）。与对照眼相比，L-IOP 眼房水中纤维化蛋白和凋亡细胞的含量更高，TGF-β1、α-SMA、纤连蛋白和裂解的 Caspase-3 的表达量明显更高（均 P < 0.05）：总之，持续两周的低眼压可能会导致TM和SC纤维化，并可能对SD大鼠眼的常规AHO不利：临床医生在治疗患者时应考虑到由房水波动引起的异常剪切力可能会损伤 AHO 流出通道。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Translational Vision Science & Technology Engineering-Biomedical Engineering

CiteScore

5.70

自引率

3.30%

发文量

346

审稿时长

25 weeks

期刊介绍： Translational Vision Science & Technology (TVST), an official journal of the Association for Research in Vision and Ophthalmology (ARVO), an international organization whose purpose is to advance research worldwide into understanding the visual system and preventing, treating and curing its disorders, is an online, open access, peer-reviewed journal emphasizing multidisciplinary research that bridges the gap between basic research and clinical care. A highly qualified and diverse group of Associate Editors and Editorial Board Members is led by Editor-in-Chief Marco Zarbin, MD, PhD, FARVO. The journal covers a broad spectrum of work, including but not limited to: Applications of stem cell technology for regenerative medicine, Development of new animal models of human diseases, Tissue bioengineering, Chemical engineering to improve virus-based gene delivery, Nanotechnology for drug delivery, Design and synthesis of artificial extracellular matrices, Development of a true microsurgical operating environment, Refining data analysis algorithms to improve in vivo imaging technology, Results of Phase 1 clinical trials, Reverse translational ("bedside to bench") research. TVST seeks manuscripts from scientists and clinicians with diverse backgrounds ranging from basic chemistry to ophthalmic surgery that will advance or change the way we understand and/or treat vision-threatening diseases. TVST encourages the use of color, multimedia, hyperlinks, program code and other digital enhancements.