Abstract
Posterior capsule opacification (PCO) is the most common complication following cataract surgery and affects millions of patients. PCO is a consequence of surgical injury promoting a wound-healing response. Following surgery, residual lens epithelial cells grow on acellular regions of the lens capsule, including the central posterior capsule. These cells can undergo fibrotic changes, such that cell transdifferentiation to myofibroblasts, matrix deposition and matrix contraction can occur, which contribute to light scatter and the need for further corrective Nd:YAG laser capsulotomy in many patients. It is therefore of great importance to better understand how PCO develops and determine better approaches to manage the condition. To achieve this, experimental systems are required, and many are available to study PCO. While there may be a number of common features associated with PCO in different species, the mechanisms governing the condition can differ. Consequently, where possible, human systems should be employed. The human capsular bag model was established in a laboratory setting on donor eyes. A capsulorhexis is performed to create an opening in the anterior capsule followed by removal of the lens fibre mass. Residual fibre cells can be removed by irrigation/aspiration and if required, an intraocular lens can be implanted. The capsular bag is isolated from the eye and transferred to a dish for culture. The human capsular bag model has played an important role in understanding the biological processes driving PCO and enables evaluation of surgical approaches, IOLs and putative therapeutic agents to better manage PCO.
摘要
后囊浑浊 (PCO) 是白内障术后最常见的并发症, 且影响着数百万患者。PCO是手术损伤后促进伤口发生愈合反应的结果。术后残余的晶状体上皮细胞在晶状体囊无细胞区域生长, 包括后囊中央区。这些细胞可发生纤维化改变, 从而使上皮细胞转分化为肌成纤维细胞, 并可能发生基质沉积和基质收缩, 这将会导致晶状体的光散射, 使许多病人需要更进一步的矫正措施—Nd: YAG激光后囊切开术。因此, 更全面地了解PCO是如何发生发展的和采取更好的措施来处理这些情况是极其重要的。为了实现这个实验, 系统是必须的, 且许多都可用于PCO的研究。虽然在不同物种中可能有许多与PCO相关的共同特点, 但控制情况的机制可以不同。因此在可能的情况下, 应采用人类 (真人的) 系统。在实验室条件下建立了供眼人类囊袋模型。实施撕囊术在前囊形成一个开口, 然后去除晶状体纤维团块。残余的纤维细胞可以通过冲洗或抽吸去除, 如果需要的话, 可植入眼内人工晶状体。将囊袋从眼中分离出来, 转移至培养皿内培养。人类囊袋模型在理解PCO生物学过程中起重要作用, 并使手术方法, 人工晶状体和假定的治疗药物的评估能更好地管理PCO。
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Wormstone IM, Eldred JA. Experimental models for posterior capsule opacification research. Exp Eye Res. 2016;142:2–12.
Eldred JA, Dawes LJ, Wormstone IM. The lens as a model for fibrotic disease. Philos Trans R Soc Lond B Biol Sci. 2011;366:1301–19.
Wormstone IM, Wang L, Liu CS. Posterior capsule opacification. Exp Eye Res. 2009;88:257–69.
Wormstone IM, Collison DJ, Hansom SP, Duncan G. A focus on the human lens in vitro. Environ Toxicol Pharm. 2006;21:215–21.
Liu CS, Wormstone IM, Duncan G, Marcantonio JM, Webb SF, Davies PD. A study of human lens cell growth in vitro. A model for posterior capsule opacification. Investig Ophthalmol Vis Sci. 1996;37:906–14.
Nagamoto T, Bissen-Miyajima H. A ring to support the capsular bag after continuous curvilinear capsulorhexis. J Cataract Refract Surg. 1994;20:417–20.
Cleary G, Spalton DJ, Zhang JJ, Marshall J. In vitro lens capsule model for investigation of posterior capsule opacification. J Cataract Refract Surg. 2010;36:1249–52.
Eldred JA, McDonald M, Wilkes HS, Spalton DJ, Wormstone IM. Growth factor restriction impedes progression of wound healing following cataract surgery: identification of VEGF as a putative therapeutic target. Sci Rep. 2016;6:24453.
Wormstone IM, Del Rio-Tsonis K, McMahon G, Tamiya S, Davies PD, Marcantonio JM, et al. FGF: An autocrine regulator of human lens cell growth independent of added stimuli. Investig Ophthalmol Vis Sci. 2001;42:1305–11.
Wormstone IM, Tamiya S, Anderson I, Duncan G. TGF-beta 2-induced matrix modification and cell transdifferentiation in the human lens capsular bag. Investig Ophthalmol Vis Sci. 2002;43:2301–8.
Wertheimer C, Kreutzer TC, Dirisamer M, Eibl-Lindner K, Kook D, Priglinger S, et al. Effect of femtosecond laser-assisted lens surgery on posterior capsule opacification in the human capsular bag in vitro. Acta Ophthalmologica. 2017;95:E85–E88.
Quinlan M, Wormstone IM, Duncan G, Davies PD. Phacoemulsification versus extracapsular cataract extraction: a comparative study of cell survival and growth on the human capsular bag in vitro. Br J Ophthalmol. 1997;81:907–10.
Eldred JA, Spalton DJ, Wormstone IM. An in vitro evaluation of the Anew Zephyr open-bag IOL in the prevention of posterior capsule opacification using a human capsular bag model. Investig Ophthalmol Vis Sci. 2014;55:7057–64.
Eldred JA, Zheng J, Chen S, Wormstone IM. An in vitro human lens capsular bag model adopting a graded culture regime to assess putative impact of IOLs on PCO formation. Investig Ophthalmol Vis Sci. 2019;60:113–22.
Wertheimer C, Kassumeh S, Piravej NP, Nilmayer O, Braun C, Priglinger C, et al. The intraocular lens as a drug delivery device: in vitro screening of pharmacologic substances for the prophylaxis of posterior capsule opacification. Investig Ophthalmol Vis Sci. 2017;58:6408–18.
Duncan G, Wang L, Neilson GJ, Wormstone IM. Lens cell survival after exposure to stress in the closed capsular bag. Investig Ophthalmol Vis Sci. 2007;48:2701–7.
Duncan G, Wormstone IM, Liu CS, Marcantonio JM, Davies PD. Thapsigargin-coated intraocular lenses inhibit human lens cell growth. Nat Med. 1997;3:1026–8.
Eldred JA, Hodgkinson LM, Dawes LJ, Reddan JR, Edwards DR, Wormstone IM. MMP2 activity is critical for TGFbeta2-induced matrix contraction–implications for fibrosis. Investig Ophthalmol Vis Sci. 2012;53:4085–98.
Smith AJO, Eldred JA, Wormstone IM. Resveratrol inhibits wound healing and lens fibrosis: a putative candidate for posterior capsule opacification prevention. Investig Ophthalmol Vis Sci. 2019;60:3863–77.
Stamer WD, Williams AM, Pflugfelder S, Coupland SE. Accessibility to and quality of human eye tissue for research: a cross-sectional survey of ARVO members. Investig Ophthalmol Vis Sci. 2018;59:4783–92.
El-Osta AA, Spalton DJ, Marshall J. In vitro model for the study of human posterior capsule opacification. J Cataract Refract Surg. 2003;29:1593–600.
Davidson MG, Harned J, Grimes AM, Duncan G, Wormstone IM, McGahan MC. Transferrin in after-cataract and as a survival factor for lens epithelium. Exp Eye Res. 1998;66:207–15.
Wormstone IM, Liu CS, Rakic JM, Marcantonio JM, Vrensen GF, Duncan G. Human lens epithelial cell proliferation in a protein-free medium. Investig Ophthalmol Vis Sci. 1997;38:396–404.
Wormstone IM, Tamiya S, Marcantonio JM, Reddan JR. Hepatocyte growth factor function and c-Met expression in human lens epithelial cells. Investig Ophthalmol Vis Sci. 2000;41:4216–22.
James C, Collison DJ, Duncan G. Characterization and functional activity of thrombin receptors in the human lens. Investig Ophthalmol Vis Sci. 2005;46:925–32.
Maidment JM, Duncan G, Tamiya S, Collison DJ, Wang L, Wormstone IM. Regional differences in tyrosine kinase receptor signaling components determine differential growth patterns in the human lens. Investig Ophthalmol Vis Sci. 2004;45:1427–35.
Leask A, Abraham DJ. TGF-beta signaling and the fibrotic response. FASEB J. 2004;18:816–27.
Derynck R, Budi EH. Specificity, versatility, and control of TGF-beta family signaling. Sci Signal. 2019;12:eaav5183.
Raghavan CT, Smuda M, Smith AJ, Howell S, Smith DG, Singh A, et al. AGEs in human lens capsule promote the TGFbeta2-mediated EMT of lens epithelial cells: implications for age-associated fibrosis. Aging Cell. 2016;15:465–76.
Wormstone IM, Anderson IK, Eldred JA, Dawes LJ, Duncan G. Short-term exposure to transforming growth factor beta induces long-term fibrotic responses. Exp Eye Res. 2006;83:1238–45.
Dawes LJ, Illingworth CD, Wormstone IM. A fully human in vitro capsular bag model to permit intraocular lens evaluation. Investig Ophthalmol Vis Sci. 2012;53:23–9.
Pande MV, Spalton DJ, Kerr-Muir MG, Marshall J. Postoperative inflammatory response to phacoemulsification and extracapsular cataract surgery: aqueous flare and cells. J Cataract Refract Surg. 1996;22:770–4.
Laurell CG, Zetterstrom C, Philipson B, Syren-Nordqvist S. Randomized study of the blood-aqueous barrier reaction after phacoemulsification and extracapsular cataract extraction. Acta Ophthalmol Scand. 1998;76:573–8.
Leishman L, Werner L, Bodnar Z, Ollerton A, Michelson J, Schmutz M, et al. Prevention of capsular bag opacification with a modified hydrophilic acrylic disk-shaped intraocular lens. J Cataract Refract Surg. 2012;38:1664–70.
Nishi O, Nishi K, Menapace R, Akura J. Capsular bending ring to prevent posterior capsule opacification: 2 year follow-up. J Cataract Refract Surg. 2001;27:1359–65.
De Groot V, Tassignon MJ, Vrensen GF. Effect of bag-in-the-lens implantation on posterior capsule opacification in human donor eyes and rabbit eyes. J Cataract Refract Surg. 2005;31:398–405.
Spalton DJ, Russell SL, Evans-Gowing R, Eldred JA, Wormstone IM. Effect of total lens epithelial cell destruction on intraocular lens fixation in the human capsular bag. J Cataract Refract Surg. 2014;40:306–12.
Tholozan FM, Gribbon C, Li Z, Goldberg MW, Prescott AR, McKie N, et al. FGF-2 release from the lens capsule by MMP-2 maintains lens epithelial cell viability. Mol Biol Cell. 2007;18:4222–31.
Mullner-Eidenbock A, Amon M, Schauersberger J, Kruger A, Abela C, Petternel V, et al. Cellular reaction on the anterior surface of 4 types of intraocular lenses. J Cataract Refract Surg. 2001;27:734–40.
Shihan MH, Novo SG, Duncan MK. Cataract surgeon viewpoints on the need for novel preventative anti-inflammatory and anti-posterior capsular opacification therapies. Curr Med Res Opin. 2019:35:1971–81.
Liu HR, Smith AJO, Ball SSR, Bao YP, Bowater RP, Wang NL, et al. Sulforaphane promotes ER stress, autophagy, and cell death: implications for cataract surgery. J Mol Med-Jmm. 2017;95:553–64.
Luft N, Kreutzer TC, Dirisamer M, Priglinger CS, Burger J, Findl O, et al. Evaluation of laser capsule polishing for prevention of posterior capsule opacification in a human ex vivo model. J Cataract Refractive Surg. 2015;41:2739–45.
D’Antin JC, Barraquer RI, Tresserra F, Michael R. Prevention of posterior capsule opacification through intracapsular hydrogen peroxide or distilled water treatment in human donor tissue. Sci Rep. 2018;8:12739.
Wertheimer C, Siedlecki J, Kook D, Mayer WJ, Wolf A, Klingenstein A, et al. EGFR inhibitor Gefitinib attenuates posterior capsule opacification in vitro and in the ex vivo human capsular bag model. Graefes Arch Clin Exp Ophthalmol. 2015;253:409–17.
Rabsilber TM, Limberger IJ, Reuland AJ, Holzer MP, Auffarth GU. Long-term results of sealed capsule irrigation using distilled water to prevent posterior capsule opacification: a prospective clinical randomised trial. Br J Ophthalmol. 2007;91:912–5.
Acknowledgements
The author would also like to thank all members of the eye research group past and present who have together with our colleagues at the Norfolk and Norwich University Hospital and around the world contributed to our evolving understanding of PCO. The efforts of the East Anglian Eye Bank, Filton Eye Bank and NHSBT are also greatly appreciated. Thanks also the generous funding bodies that have kindly supported work on the capsular bag model to date: The Humane Research Trust; British Council for the Prevention of Blindness; BBSRC; The John and Pamela Salter Trust; Cambridge Antibody Technology; Scientific Promotion of Ageing Research (SPARC); The Dunhill Medical Trust; The Lord Dowding Fund; The James Tudor Foundation; Fight for Sight; Anew Optics; Hoya Surgical Optics; Carl Zeiss Meditec AG; EPSRC.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The author declares that he has no conflict of interest.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Wormstone, I.M. The human capsular bag model of posterior capsule opacification. Eye 34, 225–231 (2020). https://doi.org/10.1038/s41433-019-0680-z
Received:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/s41433-019-0680-z
This article is cited by
-
Objective quantification of posterior capsule opacification after cataract surgery with swept-source optical coherence tomography
BMC Ophthalmology (2023)
-
Nicotinamide improves in vitro lens regeneration in a mouse capsular bag model
Stem Cell Research & Therapy (2022)
-
Moderate oxidative stress promotes epithelial–mesenchymal transition in the lens epithelial cells via the TGF-β/Smad and Wnt/β-catenin pathways
Molecular and Cellular Biochemistry (2021)
