Modeling and finite element analysis of human trabecular meshwork outflow pathways_Journal of Biomedical Engineering

Authors：

BAO Shiya , SUN Qing , CHEN Si , CHEN Xinyu , PENG Xiang ,  ZHANG Jing

School of Medical Imaging, Xuzhou Medical University, Xuzhou, Jiangsu 221004, P. R. China;

Corresponding author：

ZHANG Jing, Email: jzhang816@xzhmu.edu.cn

Keywords：

Glaucoma; Ocular hypertension; Aqueous humor outflow; Trabecular meshwork; Iris

DOI：

10.7507/1001-5515.202407037

Video：

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Glaucoma is the leading cause of irreversible blindness, primarily due to elevated intraocular pressure (IOP) resulting from increased aqueous humor outflow resistance. This study aims to establish quantitative correlations among IOP, iris mechanical properties, channel microstructures, and aqueous humor dynamics through three-dimensional modeling and finite element analysis, overcoming the limitations of conventional experimental techniques in studying aqueous flow within the trabecular meshwork (TM) outflow pathway. A three-dimensional fluid-structure interaction (FSI) model incorporating the layered TM structure, Schlemm’s canal (SC), iris, and other anterior segment tissues was developed based on human ocular anatomy. FSI simulations were performed to quantify the effects of IOP variations and iris Young's modulus on tissue morphology and aqueous humor dynamics parameters. The computational results demonstrated that axial iris deformation showed significant correlations with IOP and iris Young’s modulus. Although elevated IOP exhibited minimal effects on hydrodynamic parameters in the anterior and posterior chambers, it markedly suppressed aqueous flow velocity in the TM region. Additionally, wall shear stress in SC and collector channels displayed high sensitivity to IOP variations. These findings reveal that the tissue mechanics-FSI mechanism modulates outflow resistance by regulating aqueous humor dynamics, offering valuable references for developing clinical therapies targeting IOP reduction in glaucoma management.

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2.	刘伟, 邢小丽, 季健. 体位与眼压. 中华眼科杂志, 2015, 51(2): 146-150.
3.	Weinreb R N, Khaw P T. Primary open-angle glaucoma. Lancet, 2004, 363: 1711-1720.
4.	胡倩倩, 吴仁毅. 青光眼视神经保护的治疗现状及进展. 国际眼科杂志, 2014, 14(4): 633-636.
5.	王雪梅, 曲超. 青光眼视神经损伤的发病机制及治疗研究最新进展. 眼科新进展, 2024, 44(7): 572-577.
6.	Matlach J, Bender S, König J, et al. Investigation of intraocular pressure fluctuation as a risk factor of glaucoma progression. Clin Ophthalmol, 2019, 13: 9-16.
7.	Zhang Nan, Wang Jiaxing, Li Ying, et al. Prevalence of primary open angle glaucoma in the last 20 years: a meta-analysis and systematic review. Sci Rep, 2021, 11(1): 13762.
8.	Tamm E R. The trabecular meshwork outflow pathways: structural and functional aspects. Exp Eye Res, 2009, 88(4): 648-655.
9.	Buffault J, Labbé A, Hamard P, et al. The trabecular meshwork: Structure, function and clinical implications. A review of the literature. J Fr Ophtalmol, 2020, 43(7): 217-230.
10.	Hann C R, Fautsch M P. The elastin fiber system between and adjacent to collector channels in the human juxtacanalicular tissue. Invest Ophthalmol Vis Sci, 2011, 52(1): 45-50.
11.	McEwen W K. Application of Poiseuille's law to aqueous outflow. AMA Arch Ophthalmol, 1958, 60(2): 290-294.
12.	Kumar S, Acharya S, Beuerman R, et al. Numerical solution of ocular fluid dynamics in a rabbit eye: parametric effects. Ann Biomed Eng, 2006, 34(3): 530-544.
13.	Villamarin A, Roy S, Hasballa R, et al. 3D simulation of the aqueous flow in the human eye. Med Eng Phys, 2012, 34(10): 1462-1470.
14.	Martínez Sánchez G J, Pozo C E D, Medina J A R, et al. Numerical simulation of the aqueous humor flow in the eye drainage system; a healthy and pathological condition comparison. Med Eng Phys, 2020, 83: 82-92.
15.	Overby D R, Stamer W D, Johnson M. The changing paradigm of outflow resistance generation: Towards synergistic models of the JCT and inner wall endothelium. Exp Eye Res, 2009, 88(4): 656-670.
16.	Zhang Jing, Qian Xiuqing, Zhang Haixia, et al. Fluid-structure interaction simulation of aqueous outflow system in response to juxtacanalicular meshwork permeability changes with a two-way coupled method. CMES-Comp Model Eng, 2018, 116(2): 301-314.
17.	Zhang Jing, Qian Xiuqing, Zhang Haixia, et al. Detailed 3D micro-modeling of rat aqueous drainage channels based on two-photon imaging: simulating aqueous humor through trabecular meshwork and Schlemm’s canal by two-way fluid structure interaction approach. Med Biol Eng Comput, 2022, 60(7): 1915-1927.
18.	Strohmaier C A, Reitsamer H A, Kiel J W. Episcleral venous pressure and IOP responses to central electrical stimulation in the rat. Invest Ophthalmol Vis Sci, 2013, 54(10): 6860-6866.
19.	Hashemi H, Kashi A H, Fotouhi A, et al. Distribution of intraocular pressure in healthy Iranian individuals: the Tehran Eye Study. Br J Ophthalmol, 2005, 89(6): 652-657.
20.	黄颖, 邸悦, 乔彤. 豚鼠与人眼球结构及生物学参数的比较研究进展. 中国眼耳鼻喉科杂志, 2023, 23(2): 180-184.
21.	Wang Wenjia, Qian Xiuqing, Song Hongfang, et al. Fluid and structure coupling analysis of the interaction between aqueous humor and iris. Biomed Eng Online, 2016, 15(Suppl 2): 569-586.
22.	钱秀清, 宋红芳, 刘志成. 青光眼生物力学研究进展. 科技导报, 2018, 36(13): 30-38.
23.	Mei Xi, Ren Lin, Xu Qiang, et al. Effect of persistent high intraocular pressure on microstructure and hydraulic permeability of trabecular meshwork. Chin Phys B, 2015, 24(5): 610-617.
24.	Gerlach J C, Hentschel F, Spatkowski G, et al. Cell detachment during sinusoidal reperfusion after liver preservation: an in vitro model. Transplantation, 1997, 64(6): 907-912.
25.	Doors M, Berendschot T T, Webers C A, et al. Model to predict endothelial cell loss after iris-fixated phakic intraocular lens implantation. Invest Ophthalmol Vis Sci, 2010, 51(2): 811-815.
26.	Malek A M, Alper S L, Izumo S. Hemodynamic shear stress and its role in atherosclerosis. JAMA, 1999, 282(21): 2035-2042.
27.	Byfield F J, Wen Q, Levental I, et al. Absence of filamin A prevents cells from responding to stiffness gradients on gels coated with collagen but not fibronectin. Biophys J, 2009, 96(12): 5095-5102.
28.	Solon J, Levental I, Sengupta K, et al. Fibroblast adaptation and stiffness matching to soft elastic substrates. Biophys J, 2007, 93(12): 4453-4461.
29.	张迪, 张海霞, 李林. 基于快速加卸载的单轴拉伸识别屈光术后兔角膜的生物力学特性. 生物医学工程学杂志, 2024, 41(1): 136-143.
30.	王川, 董建鑫, 张静, 等. 大鼠小梁网组织压痕实验有限元模拟研究. 北京生物医学工程, 2022, 41(5): 454-457,464.
31.	Vranka J A, Staverosky J A, Reddy A P, et al. Biomechanical rigidity and quantitative proteomics analysis of segmental regions of the trabecular meshwork at physiologic and elevated pressures. Invest Ophthalmol Vis Sci, 2018, 59(1): 246-259.
32.	Karimi A, Khan S, Razaghi R, et al. Segmental biomechanics of the normal and glaucomatous human aqueous outflow pathway. Acta Biomaterialia, 2024, 173: 148-166.

1. Tham Y C, Li X, Wong T Y. Global prevalence of glaucoma and projections of glaucoma burden through 2040: a systematic review and meta-analysis. Ophthalmology, 2014, 121(11): 2081-2090.
2. 刘伟, 邢小丽, 季健. 体位与眼压. 中华眼科杂志, 2015, 51(2): 146-150.
3. Weinreb R N, Khaw P T. Primary open-angle glaucoma. Lancet, 2004, 363: 1711-1720.
4. 胡倩倩, 吴仁毅. 青光眼视神经保护的治疗现状及进展. 国际眼科杂志, 2014, 14(4): 633-636.
5. 王雪梅, 曲超. 青光眼视神经损伤的发病机制及治疗研究最新进展. 眼科新进展, 2024, 44(7): 572-577.
6. Matlach J, Bender S, König J, et al. Investigation of intraocular pressure fluctuation as a risk factor of glaucoma progression. Clin Ophthalmol, 2019, 13: 9-16.
7. Zhang Nan, Wang Jiaxing, Li Ying, et al. Prevalence of primary open angle glaucoma in the last 20 years: a meta-analysis and systematic review. Sci Rep, 2021, 11(1): 13762.
8. Tamm E R. The trabecular meshwork outflow pathways: structural and functional aspects. Exp Eye Res, 2009, 88(4): 648-655.
9. Buffault J, Labbé A, Hamard P, et al. The trabecular meshwork: Structure, function and clinical implications. A review of the literature. J Fr Ophtalmol, 2020, 43(7): 217-230.
10. Hann C R, Fautsch M P. The elastin fiber system between and adjacent to collector channels in the human juxtacanalicular tissue. Invest Ophthalmol Vis Sci, 2011, 52(1): 45-50.
11. McEwen W K. Application of Poiseuille's law to aqueous outflow. AMA Arch Ophthalmol, 1958, 60(2): 290-294.
12. Kumar S, Acharya S, Beuerman R, et al. Numerical solution of ocular fluid dynamics in a rabbit eye: parametric effects. Ann Biomed Eng, 2006, 34(3): 530-544.
13. Villamarin A, Roy S, Hasballa R, et al. 3D simulation of the aqueous flow in the human eye. Med Eng Phys, 2012, 34(10): 1462-1470.
14. Martínez Sánchez G J, Pozo C E D, Medina J A R, et al. Numerical simulation of the aqueous humor flow in the eye drainage system; a healthy and pathological condition comparison. Med Eng Phys, 2020, 83: 82-92.
15. Overby D R, Stamer W D, Johnson M. The changing paradigm of outflow resistance generation: Towards synergistic models of the JCT and inner wall endothelium. Exp Eye Res, 2009, 88(4): 656-670.
16. Zhang Jing, Qian Xiuqing, Zhang Haixia, et al. Fluid-structure interaction simulation of aqueous outflow system in response to juxtacanalicular meshwork permeability changes with a two-way coupled method. CMES-Comp Model Eng, 2018, 116(2): 301-314.
17. Zhang Jing, Qian Xiuqing, Zhang Haixia, et al. Detailed 3D micro-modeling of rat aqueous drainage channels based on two-photon imaging: simulating aqueous humor through trabecular meshwork and Schlemm’s canal by two-way fluid structure interaction approach. Med Biol Eng Comput, 2022, 60(7): 1915-1927.
18. Strohmaier C A, Reitsamer H A, Kiel J W. Episcleral venous pressure and IOP responses to central electrical stimulation in the rat. Invest Ophthalmol Vis Sci, 2013, 54(10): 6860-6866.
19. Hashemi H, Kashi A H, Fotouhi A, et al. Distribution of intraocular pressure in healthy Iranian individuals: the Tehran Eye Study. Br J Ophthalmol, 2005, 89(6): 652-657.
20. 黄颖, 邸悦, 乔彤. 豚鼠与人眼球结构及生物学参数的比较研究进展. 中国眼耳鼻喉科杂志, 2023, 23(2): 180-184.
21. Wang Wenjia, Qian Xiuqing, Song Hongfang, et al. Fluid and structure coupling analysis of the interaction between aqueous humor and iris. Biomed Eng Online, 2016, 15(Suppl 2): 569-586.
22. 钱秀清, 宋红芳, 刘志成. 青光眼生物力学研究进展. 科技导报, 2018, 36(13): 30-38.
23. Mei Xi, Ren Lin, Xu Qiang, et al. Effect of persistent high intraocular pressure on microstructure and hydraulic permeability of trabecular meshwork. Chin Phys B, 2015, 24(5): 610-617.
24. Gerlach J C, Hentschel F, Spatkowski G, et al. Cell detachment during sinusoidal reperfusion after liver preservation: an in vitro model. Transplantation, 1997, 64(6): 907-912.
25. Doors M, Berendschot T T, Webers C A, et al. Model to predict endothelial cell loss after iris-fixated phakic intraocular lens implantation. Invest Ophthalmol Vis Sci, 2010, 51(2): 811-815.
26. Malek A M, Alper S L, Izumo S. Hemodynamic shear stress and its role in atherosclerosis. JAMA, 1999, 282(21): 2035-2042.
27. Byfield F J, Wen Q, Levental I, et al. Absence of filamin A prevents cells from responding to stiffness gradients on gels coated with collagen but not fibronectin. Biophys J, 2009, 96(12): 5095-5102.
28. Solon J, Levental I, Sengupta K, et al. Fibroblast adaptation and stiffness matching to soft elastic substrates. Biophys J, 2007, 93(12): 4453-4461.
29. 张迪, 张海霞, 李林. 基于快速加卸载的单轴拉伸识别屈光术后兔角膜的生物力学特性. 生物医学工程学杂志, 2024, 41(1): 136-143.
30. 王川, 董建鑫, 张静, 等. 大鼠小梁网组织压痕实验有限元模拟研究. 北京生物医学工程, 2022, 41(5): 454-457,464.
31. Vranka J A, Staverosky J A, Reddy A P, et al. Biomechanical rigidity and quantitative proteomics analysis of segmental regions of the trabecular meshwork at physiologic and elevated pressures. Invest Ophthalmol Vis Sci, 2018, 59(1): 246-259.
32. Karimi A, Khan S, Razaghi R, et al. Segmental biomechanics of the normal and glaucomatous human aqueous outflow pathway. Acta Biomaterialia, 2024, 173: 148-166.

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