Mechanical property changes of glial LC and RGC axons in response to high intraocular pressure.

IF 4.3 3区工程技术 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Frontiers in Bioengineering and Biotechnology Pub Date : 2025-04-28 eCollection Date: 2025-01-01 DOI:10.3389/fbioe.2025.1574231

Bochao Ma, Liu Liu, Yushu Liu, Jifeng Ren, Xiuqing Qian

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引用次数: 0

Abstract

Introduction: Pathological high intraocular pressure (IOP) is an important risk factor for glaucoma. The lamina cribrosa (LC) area in the optic nerve head is the initial site of optic nerve injury for glaucoma. LC deformation caused by elevated IOP will compress the retinal ganglion cells (RGC) axons passing through it, thereby leading to the damage of the RGC axons. The deformation of LC is highly correlated with its mechanical properties. Therefore, changes in mechanical properties of LC with the duration of high IOP is of great significance.

Methods: To investigate the impact of chronic high IOP on the mechanical properties of the LC, rat models were established by cauterizing the superior scleral vein and injecting 5-fluorouracil (5-FU) under the conjunctiva to maintain elevated IOP. The linear elastic properties of the glial LC and RGC axons in affected eyes were measured using atomic force microscopy (AFM) combined with image segmentation techniques. Morphological alterations of the glial LC were assessed using hematoxylin-eosin staining, immunofluorescence staining, and transmission electron microscopy (TEM).

Results: Compared to the control group, the Young's modulus of the glial LC decreased by 35.5%, 74.2%, and 80.6% at 4, 8, and 12 weeks of elevated IOP, respectively. Similarly, the Young's modulus of RGC axons decreased by 45.6%, 70.9%, and 75.9% over the same time points. These findings demonstrate a time-dependent reduction in the mechanical stiffness of both glial LC and RGC axons under chronic high IOP conditions.

Discussion: The progressive decrease in Young's modulus indicated that prolonged high IOP compromises the structural integrity and mechanical properties of the LC and RGC axons. This mechanical weakening likely contributes to the pathophysiological process of optic nerve injury in glaucoma. The present study offers important insights into the biomechanical mechanisms underlying glaucomatous damage, which may guide future research and therapeutic strategies.

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高眼压对神经胶质LC和RGC轴突力学特性的影响。

病理性高眼压（IOP）是青光眼的重要危险因素。视神经头的网层（LC）区是青光眼视神经损伤的起始部位。IOP升高引起的LC变形会压迫通过它的视网膜神经节细胞（RGC）轴突，从而导致RGC轴突的损伤。LC的变形与其力学性能密切相关。因此，LC力学性能随高眼压持续时间的变化具有重要意义。方法：采用烧灼巩膜上静脉并在结膜下注射5-氟尿嘧啶（5-FU）维持高IOP的方法建立大鼠模型，探讨慢性高IOP对LC力学性能的影响。采用原子力显微镜（AFM）结合图像分割技术测量了眼内神经胶质LC和RGC轴突的线弹性特性。采用苏木精-伊红染色、免疫荧光染色和透射电镜（TEM）观察胶质细胞LC的形态学变化。结果：与对照组相比，在IOP升高4、8和12周时，胶质细胞LC的杨氏模量分别下降了35.5%、74.2%和80.6%。同样，RGC轴突的杨氏模量在相同时间点上分别下降了45.6%、70.9%和75.9%。这些发现表明，在慢性高IOP条件下，胶质LC和RGC轴突的机械刚度随时间降低。杨氏模量的逐渐下降表明，长时间的高IOP损害了LC和RGC轴突的结构完整性和力学性能。这种机械弱化可能参与了青光眼视神经损伤的病理生理过程。本研究对青光眼损伤的生物力学机制提供了重要的见解，可能指导未来的研究和治疗策略。

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

Frontiers in Bioengineering and Biotechnology Chemical Engineering-Bioengineering

CiteScore

8.30

自引率

5.30%

发文量

2270

审稿时长

12 weeks

期刊介绍： The translation of new discoveries in medicine to clinical routine has never been easy. During the second half of the last century, thanks to the progress in chemistry, biochemistry and pharmacology, we have seen the development and the application of a large number of drugs and devices aimed at the treatment of symptoms, blocking unwanted pathways and, in the case of infectious diseases, fighting the micro-organisms responsible. However, we are facing, today, a dramatic change in the therapeutic approach to pathologies and diseases. Indeed, the challenge of the present and the next decade is to fully restore the physiological status of the diseased organism and to completely regenerate tissue and organs when they are so seriously affected that treatments cannot be limited to the repression of symptoms or to the repair of damage. This is being made possible thanks to the major developments made in basic cell and molecular biology, including stem cell science, growth factor delivery, gene isolation and transfection, the advances in bioengineering and nanotechnology, including development of new biomaterials, biofabrication technologies and use of bioreactors, and the big improvements in diagnostic tools and imaging of cells, tissues and organs. In today`s world, an enhancement of communication between multidisciplinary experts, together with the promotion of joint projects and close collaborations among scientists, engineers, industry people, regulatory agencies and physicians are absolute requirements for the success of any attempt to develop and clinically apply a new biological therapy or an innovative device involving the collective use of biomaterials, cells and/or bioactive molecules. “Frontiers in Bioengineering and Biotechnology” aspires to be a forum for all people involved in the process by bridging the gap too often existing between a discovery in the basic sciences and its clinical application.