切换至 "中华医学电子期刊资源库"
高级检索
中华眼科医学杂志(电子版)

中华眼科医学杂志(电子版) ›› 2019, Vol. 09 ›› Issue (02) : 118 -123. doi: 10.3877/cma.j.issn.2095-2007.2019.02.009

综述

角膜内皮细胞相关基础及临床研究的现状
苏冠羽1, 王乐滢1, 梁庆丰1,†()   
  1. 1. 100730　首都医科大学附属北京同仁医院　北京同仁眼科中心　北京市眼科研究所　北京市眼科学与视觉科学重点实验室
  • 收稿日期:2019-04-17 出版日期:2019-04-28
  • 通信作者: 梁庆丰
  • 基金资助:
    北京市卫生系统高层次卫生技术人才培养基金(2014-3-016); 国家重点研发计划项目(2017YFB1302703)

The corneal endothelial cells related basic and clinical research status

Guanyu Su1, Leying Wang1, Qingfeng Liang1,†()   

  1. 1. Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Institute of Ophthalmology, Beijing Keynote Laboratory of Ophthalmology and Visual Science, Beijing 100730, China
  • Received:2019-04-17 Published:2019-04-28
  • Corresponding author: Qingfeng Liang
全文 ( ) 下载PDF ( ) 导出引用
引用本文：

苏冠羽, 王乐滢, 梁庆丰. 角膜内皮细胞相关基础及临床研究的现状[J]. 中华眼科医学杂志(电子版), 2019, 09(02): 118-123.

Guanyu Su, Leying Wang, Qingfeng Liang. The corneal endothelial cells related basic and clinical research status[J]. Chinese Journal of Ophthalmologic Medicine(Electronic Edition), 2019, 09(02): 118-123.

角膜内皮细胞(HCECs)是保证角膜透明的重要结构，在角膜后弹力层和前房之间，具有屏障和离子泵功能，防止前房房水进入角膜的同时又可以将角膜基质中的水分转移至前房，维持角膜正常厚度。当HCECs损伤、密度下降到一定程度时，这种平衡被打破，就会产生角膜水肿等角膜疾病。因此，HCECs在角膜组织解剖中的作用十分重要。此外，目前在体HCECs是不可再生的，一旦损害，视力将会严重受损。本文中笔者就HCECs的正常生理、损伤机制、检测、治疗及再生的研究情况进行综述。

关键词: 角膜内皮细胞, 损伤机制, 检测, 治疗, 再生

The corneal endothelial cells (HCECs) are an important structure to ensure corneal transparency, with functions of barrier and ion pump between entocornea and anterior chamber which could prevent anterior chamber aqueous humor into cornea; at the same time, transfer moisture in the corneal stroma to the anterior chamber to maintaine normal thickness of cornea. HCECs once were damaged, can decrease their density to a certain extent. And with the unbalance going on, the disease could be with the symptom of corneal edema, etc. Therefore, HCECs play a extremely important role in corneal anatomy. Additionally, HCECs are non-renewable in vivo and serious loss of vision are non-recovered if damaged. This paper reviews the current status of the normal physiology, damage mechanism, detection, treatment, and regeneration of HCECs.

Key words: Human corneal endothelial cells (HCECs), Damage mechanism, Detection, Treatment, Regeneration
图1 非接触角膜内皮镜成像及活体共聚焦显微镜成像　图A为角膜内皮镜对角膜内皮的评估界面；图B为活体共聚焦显微镜显示角膜内皮细胞的大小、形态结构
[1]
Peh GS, Beuerman RW, Colman A, et al. Human corneal endothelial cell expansion for corneal endothelium transplantation: an overview[J]. Transplantation, 2011, 91(8): 811-819.
[2]
De Miguel MP, Alio JL, Arnalich-Montiel F, et al. Cornea and ocular surface treatment[J]. Curr Stem Cell Res Ther, 2010, 5(2): 195-204.
[3]
Adamis AP, Molnar ML, Tripathi BJ, et al. Neuronal-specific enolase in human corneal endothelium and posterior keratocytes[J]. Exp Eye Res, 1985, 41(5): 665-668.
[4]
Speedwell L, Novakovic P, Sherrard ES, et al. The infant corneal endothelium[J]. Arch Ophthalmol, 1988, 106(6): 771-775.
[5]
Nucci P, Brancato R, Mets MB, et al. Normal endothelial cell density range in childhood[J]. Arch Ophthalmol, 1990, 108(2): 247-248.
[6]
Bourne WM, Nelson LR, Hodge DO. Central corneal endothelial cell changes over a ten-year period[J]. Invest Ophthalmol Vis Sci, 1997, 38(3): 779-782.
[7]
Joyce NC. Proliferative capacity of corneal endothelial cells[J]. Exp Eye Res, 2012, 95(1): 16-23.
[8]
姜雪，李昕悦，孙婉彤，等. 角膜内皮细胞的检测、受损因素及治疗新进展[J]. 现代生物医学进展，2018，18(1)：195-200.
[9]
Yang R, Sha X, Zeng M, et al. The influence of phacoemulsification on corneal endothelial cells at varying blood glucose levels[J]. Eye Sci, 2011, 26(2): 91-95.
[10]
Urban B, Raczyńska D, Bakunowicz-Łazarczyk A, et al. Evaluation of corneal endothelium in children and adolescents with type 1 diabetes mellitus[J]. Mediators Inflamm, 2013, 2013(3): 913754.
[11]
王琳. 不同分级原发性高血压对角膜内皮细胞的影响[J]. 国际眼科杂志，2015(12)：2140-2142.
[12]
李进容，刘苏，王茜，等. 代谢综合征对角膜内皮细胞形态学影响的临床研究[J]. 中华眼科医学杂志(电子版), 2016, 6(2)：68-74.
[13]
Sati A, Jha A, Moulick PS, et al. Corneal endothelial alterations in chronic renal failure[J]. Cornea, 2016, 35(10): 1320-1325.
[14]
Gipson IK. Age-related changes and diseases of the ocular surface and cornea[J]. Invest Ophthalmol Vis Sci, 2013, 54(14): 48-53.
[15]
Eghrari AO, Riazuddin SA, Gottsch JD. Fuchs corneal dystrophy[J]. Prog Mol Biol Transl Sci, 2015, 134: 79-97.
[16]
杜飞. 角膜内皮细胞形态学的研究进展[J]. 外科研究与新技术，2013, 2(2)：113-118.
[17]
Marta S, Flavio M, , Marco M , et al. Diagnosis and management of iridocorneal endothelial syndrome[J]. Biomed Res Int, 2015, 2015: 1-9.
[18]
Serrao S, Lombardo M. Corneal endothelial damage after simultaneous PRK and corneal cross-linking in stable keratoconus[J]. Am J Ophthalmol Case Rep, 2019, 14: 32-34.
[19]
Storr-Paulsen A, Norregaard JC, Ahmed S, et al. Endothelial cell damage after cataract surgery: divide-and-conquer versus phaco-chop technique[J]. J Cataract Refract Surg, 2008, 34(6): 996-1000.
[20]
Obata H, Murao M, Miyata K, et al. Corneal endothelial cell damage in penetrating keratoplasty[J]. Nippon Ganka Gakkai Zasshi, 1992, 96(3): 346-351.
[21]
Janson BJ, Alward WL, Kwon YH, et al. Glaucoma-associated corneal endothelial cell damage: a review[J]. Surv Ophthalmol, 2018, 63(4): 500-506.
[22]
詹磊，熊思盈，甘孟欣，等. 玻璃体切割联合白内障手术对DR患者角膜内皮细胞的影响[J]. 国际眼科杂志，2017, 17(8)：1529-1531.
[23]
Cinar E, Zengin MO, Kucukerdonmez C. Evaluation of corneal endothelial cell damage after vitreoretinal surgery: comparison of different endotamponades[J]. Eye (Lond), 2015, 29(5): 670-674.
[24]
Patel SV. Graft survival and endothelial outcomes in the new era of endothelial keratoplasty[J]. Exp Eye Res, 2012, 95(1): 40-47.
[25]
Kwon J, Heo JH, Kim HM, et al. Comparison of cytotoxic effects on rabbit corneal endothelium between preservative-free and preservative-containing dorzolamide/timolol[J]. Korean J Ophthalmol, 2015, 29(5): 344-350.
[26]
Zimmermann N, Wünscher M, Schlötzer-Schrehardt U, et al. Corneal endothelial cell density and its correlation with the severity of pseudoexfoliation[J]. Klin Monbl Augenheilkd, 2014, 231(2): 158-163.
[27]
Yahata Y, Murakami S, Hashimoto K. A new histamine measurement system employing a confocal laser microscope and cultured human dermal microvascular endothelial cells[J]. J Dermatol Sci, 2003, 32(3): 201-207.
[28]
Zheng T, Le Q, Hong J, et al. Comparison of human corneal cell density by age and corneal location: an in vivo confocal microscopy study[J]. BMC Ophthalmol, 2016, 16(1): 109.
[29]
Yoshihara M, Ohmiya H, Hara S, et al. Discovery of molecular markers to discriminate corneal endothelial cells in the human body[J]. PLoS One, 2015, 10(3): e0117581.
[30]
Chen J, Li Z, Zhang L, et al. Descemet′s membrane supports corneal endothelial cell regeneration in rabbits[J]. Sci Rep, 2017, 7(1): 6983.
[31]
Ide T, Yoo SH, Kymionis GD, et al. Descemet-stripping automated endothelial keratoplasty (DSAEK): effect of nontoxic gentian violet marking pen on DSAEK donor tissue viability by using vital dye assay[J]. Cornea, 2008, 27(5): 562-564.
[32]
Bostan C, Thériault M, Forget KJ, et al. In vivo functionality of a corneal endothelium transplanted by cell-injection therapy in a feline model[J]. Invest Ophthalmol Vis Sci, 2016, 57(4): 1620-1634.
[33]
廉井财，顾丽琼，石海云，等. 兔眼LASIK手术前后角膜表面超微结构变化和角膜神经染色观察[J]. 眼科研究，2010, 28(2)：109-113.
[34]
郑鑫，麻伟南，叶春华. 丝裂霉素C对白内障合并青光眼患者角膜内皮细胞的影响[J]. 国际眼科杂志，2018, 18(1)：96-99.
[35]
Koizumi N, Okumura N, Ueno M, et al. New therapeutic modality for corneal endothelial disease using Rho-associated kinase inhibitor eye drops[J]. Cornea, 2014, 33(11): S25-S31.
[36]
Alió Del Barrio JL, Vargas V. Femtosecond laser-assisted deep lamellar descemet membrane endothelial keratoplasty for the treatment of endothelial dysfunction associated with posterior stromal scarring[J]. Cornea, 2019, 38(3): 388-391.
[37]
赵长霖，薛春燕，徐欢欢，等. 飞秒激光辅助角膜内皮移植术治疗大泡性角膜病变的疗效观察[J]. 国际眼科杂志，2016, 16(2)：335-338.
[38]
Price MO, Price FW. Descemet's membrane endothelial keratoplasty surgery: update on the evidence and hurdles to acceptance[J]. Curr Opin Ophthalmol, 2013, 24(4): 329-335.
[39]
Anshu A, Price MO, Price FW. Risk of corneal transplant rejection significantly reduced with Descemet's membrane endothelial keratoplasty[J]. Ophthalmology, 2012, 119(3): 536-540.
[40]
Singh NP, Said DG, Dua HS. Lamellar keratoplasty techniques[J]. Indian J Ophthalmol, 2018, 66(9): 1239-1250.
[41]
Fuest M, Yam GH, Peh GS, et al. Advances in corneal cell therapy[J]. Regen Med, 2016, 11(6): 601-615.
[42]
Fan T, Ma X, Zhao J, et al. Transplantation of tissue-engineered human corneal endothelium in cat models[J]. Mol Vis, 2013, 19: 400-407.
[43]
Petroll WM, Jester JV, Bean JJ, et al. Myofibroblast transformation of cat corneal endothelium by transforming growth factor-beta1, -beta2, and -beta3[J]. Invest Ophthalmol Vis Sci, 1998, 39(11): 2018-2032.
[44]
Chen KH, Azar D, Joyce NC. Transplantation of adult human corneal endothelium ex vivo: a morphologic study[J]. Cornea, 2001, 20(7): 731-737.
[45]
Li W, Sabater AL, Chen YT, et al. A novel method of isolation, preservation, and expansion of human corneal endothelial cells[J]. Invest Ophthalmol Vis Sci, 2007, 48(2): 614-620.
[46]
Lee JG, Kay EP. FGF-2-mediated signal transduction during endothelial mesenchymal transformation in corneal endothelial cells[J]. Exp Eye Res, 2006, 83(6): 1309-1316.
[47]
Hatou S, Yoshida S, Higa K, et al. Functional corneal endothelium derived from corneal stroma stem cells of neural crest origin by retinoic acid and Wnt/β-catenin signaling[J]. Stem Cells Dev, 2013, 22(5): 828-839.
[48]
Joyce NC, Harris DL. Decreasing expression of the G1-phase inhibitors, p21Cip1 and p16INK4a, promotes division of corneal endothelial cells from older donors[J]. Mol Vis, 2010, 16: 897-906.
[49]
Treffers WF. Human corneal endothelial wound repair. In vitro and in vivo[J]. Ophthalmology, 1982, 89(6): 605-613.
[50]
Joyce NC, Zhu CC. Human corneal endothelial cell proliferation: potential for use in regenerative medicine[J]. Cornea, 2004, 23(8): S8-S19.
[51]
Okumura N, Koizumi N, Ueno M, et al. ROCK inhibitor converts corneal endothelial cells into a phenotype capable of regenerating in vivo endothelial tissue[J]. Am J Pathol, 2012, 181(1): 268-277.
[52]
Okumura N, Koizumi N, Kay EP, et al. The ROCK inhibitor eye drop accelerates corneal endothelium wound healing[J]. Invest Ophthalmol Vis Sci, 2013, 54(4): 2493-2502.
[53]
Peh GS, Toh KP, Wu FY, et al. Cultivation of human corneal endothelial cells isolated from paired donor corneas[J]. PLoS One, 2011, 6(12): e28310.
[54]
Chen KH, Harris DL, Joyce NC. TGF-beta2 in aqueous humor suppresses S-phase entry in cultured corneal endothelial cells[J]. Invest Ophthalmol Vis Sci, 1999, 40(11): 2513-2519.
[55]
Kim TY, Kim WI, Smith RE, et al. Role of p27(Kip1) in cAMP- and TGF-beta2-mediated antiproliferation in rabbit corneal endothelial cells[J]. Invest Ophthalmol Vis Sci, 2001, 42(13): 3142-3149.
[56]
Wendt MK, Allington TM, Schiemann WP. Mechanisms of the epithelial-mesenchymal transition by TGF-beta[J]. Future Oncol, 2009, 5(8): 1145-1168.
[57]
Kaimori A, Potter J, Kaimori JY, et al. Transforming growth factor-beta1 induces an epithelial-to-mesenchymal transition state in mouse hepatocytes in vitro[J]. J Biol Chem, 2007, 282(30): 22089-22101.
[58]
Basu S, Hertsenberg AJ, Funderburgh ML, et al. Human limbal biopsy-derived stromal stem cells prevent corneal scarring[J]. Sci Transl Med, 2014, 6(266): 266ra172.
[59]
Raj A, Girgis RA. Increased endothelial cell density in the paracentral and peripheral regions of the human cornea[J]. Am J Ophthalmol, 2003, 136(4): 774-775.
[60]
Zhu C, Joyce NC. Proliferative response of corneal endothelial cells from young and older donors[J]. Invest Ophthalmol Vis Sci, 2004, 45(6): 1743-1751.
[61]
Palchesko RN, Funderburgh JL, Feinberg AW. Engineered basement membranes for regenerating the corneal endothelium[J]. Adv Healthc Mater, 2016, 5(22): 2942-2950.
[62]
Senoo T, Obara Y, Joyce NC. EDTA: a promoter of proliferation in human corneal endothelium[J]. Invest Ophthalmol Vis Sci, 2000, 41(10): 2930-2935.
[63]
Zhu YT, Hayashida Y, Kheirkhah A, et al. Characterization and comparison of intercellular adherent junctions expressed by human corneal endothelial cells in vivo and in vitro[J]. Invest Ophthalmol Vis Sci, 2008, 49(9): 3879-3886.
[64]
Brunst VV. Successive changes in the cornea of young axolotl (siredon mexicanum) after X-irradiation[J]. Radiat Res, 1963, 20(3): 325-340.
[65]
Bredow L, Schwartzkopff J, Reinhard T. Host-derived endothelial regeneration of corneal transplants in a rat keratoplasty model[J]. Ophthalmic Res, 2014, 52(2): 60-64.
[66]
Schwartzkopff J, ，Bredow L, Mahlenbrey S, et al. Regeneration of corneal endothelium following complete endothelial cell loss in rat keratoplasty[J]. Mol Vis, 2010, 11(16): 2368-2375.
[67]
Cornell LE, Wehmeyer JL, Johnson AJ, et al. Magnetic nanoparticles as a potential vehicle for corneal endothelium repair[J]. Mil Med, 2016, 181(5): 232-239.
[68]
Kielbowicz Z, Kuryszko J, Strzadaa L. Experimental allogenic transplantation of cornea endothelial cells in cats[J]. Pol J Vet Sci, 2010, 13(4): 731-741.
[69]
Nakahori Y, Katakami C, Yamamoto M. Corneal endothelial cell proliferation and migration after penetrating keratoplasty in rabbits[J]. Jpn J Ophthalmol, 1996, 40(2): 271-278.
[70]
Ozcelik B, Brown KD, Blencowe A, et al. Biodegradable and biocompatible poly(ethylene glycol)-based hydrogel films for the regeneration of corneal endothelium[J]. Adv Healthc Mater, 2014, 3(9): 1496-1507.
[71]
Heur M, Jiao S, , Schindler S , et al. Regenerative potential of the zebrafish corneal endothelium[J]. Exp Eye Res, 2013, 106：1-4.
[72]
Kim do K, Sim BR, Khang G. Nature-derived aloe vera gel blended silk fibroin film scaffolds for cornea endothelial cell regeneration and transplantation[J]. ACS Appl Mater Interfaces, 2016, 8(24): 15160-15168.
[73]
Galvis V, Tello A, Miotto G. Human corneal endothelium regeneration[J]. Ophthalmology, 2012, 119(8): 1714-1715.
[74]
Shah RD, Randleman JB, Grossniklaus HE. Spontaneous corneal clearing after Descemet′s stripping without endothelial replacement[J]. Ophthalmology, 2012, 119(2): 256-260.
[75]
Pipparelli A, Arsenijevic Y, Thuret G, et al. ROCK inhibitor enhances adhesion and wound healing of human corneal endothelial cells[J]. PLoS One, 2013, 8(4): e62095.
[76]
Jullienne R, Manoli P, Tiffet T, et al. Corneal endothelium self-healing mathematical model after inadvertent descemetorhexis[J]. J Cataract Refract Surg, 2015, 41(10): 2313-2318.
[77]
Soh YQ, Mehta JS. Regenerative therapy for fuchs endothelial corneal dystrophy[J]. Cornea, 2018, 37(4): 523-527.
[1] 王得晨, 杨康, 杨自杰, 归明彬, 屈莲平, 张小凤, 高峰. 结直肠癌微卫星稳定状态和程序性死亡、吲哚胺2,3-双加氧酶关系的研究进展[J]. 中华普通外科学文献(电子版), 2023, 17(06): 462-465.
[2] 叶晓琳, 刘云飞, 庞明泉, 王海久, 任利, 侯立朝, 于文昊, 王志鑫, 樊海宁. 肝再生细胞来源及调控机制的研究进展[J]. 中华普外科手术学杂志(电子版), 2024, 18(01): 96-99.
[3] 彭旭, 邵永孚, 李铎, 邹瑞, 邢贞明. 结肠肝曲癌的诊断和外科治疗[J]. 中华普外科手术学杂志(电子版), 2024, 18(01): 108-110.
[4] 马伟强, 马斌林, 吴中语, 张莹. microRNA在三阴性乳腺癌进展中发挥的作用[J]. 中华普外科手术学杂志(电子版), 2024, 18(01): 111-114.
[5] 樊丽超, 郭瑾瑛, 陈鑫. 野生型RET与RET/PTC融合基因检测对甲状腺乳头状癌中央区淋巴结清扫的指导意义[J]. 中华普外科手术学杂志(电子版), 2023, 17(06): 631-635.
[6] 张海涛, 康婵娟, 翟静洁. 胰管支架置入治疗急性胆源性胰腺炎效果观察[J]. 中华普外科手术学杂志(电子版), 2023, 17(06): 654-657.
[7] 杨雪, 张伟, 尚培中, 宋创业, 尚丹丹, 张蔚. 胆囊十二指肠瘘结石经瘘口排出后自愈一例报道[J]. 中华普外科手术学杂志(电子版), 2023, 17(06): 707-708.
[8] 孔博, 张璟, 吕珂. 超声技术在复杂腹壁疝诊治中的作用[J]. 中华疝和腹壁外科杂志(电子版), 2023, 17(06): 670-673.
[9] 姜明, 罗锐, 龙成超. 闭孔疝的诊断与治疗：10年73例患者诊疗经验总结[J]. 中华疝和腹壁外科杂志(电子版), 2023, 17(06): 706-710.
[10] 魏小勇. 原发性肝癌转化治疗焦点问题探讨[J]. 中华肝脏外科手术学电子杂志, 2023, 12(06): 602-607.
[11] 辛彩焕, 熊辉. 非疫区36例布鲁菌病患者的临床特征及诊疗分析[J]. 中华临床医师杂志(电子版), 2023, 17(9): 927-931.
[12] 陆志峰, 周佳佳, 梁舒. 虚拟现实技术在治疗弱视中的临床应用研究进展[J]. 中华临床医师杂志(电子版), 2023, 17(08): 891-895.
[13] 李田, 徐洪, 刘和亮. 尘肺病的相关研究进展[J]. 中华临床医师杂志(电子版), 2023, 17(08): 900-905.
[14] 岳瑞雪, 孔令欣, 郝鑫, 杨进强, 韩猛, 崔国忠, 王建军, 张志生, 孔凡庭, 张维, 何文博, 李现桥, 周新平, 徐东宏, 胡崇珠. 乳腺癌HER2蛋白表达水平预测新辅助治疗疗效的真实世界研究[J]. 中华临床医师杂志(电子版), 2023, 17(07): 765-770.
[15] 符梅沙, 周玉华, 李慧, 薛春颜. 淋巴细胞免疫治疗对复发性流产患者外周血T淋巴细胞亚群分布与PD1/PD-L1表达的影响及意义[J]. 中华临床医师杂志(电子版), 2023, 17(06): 726-730.
阅读次数
全文


摘要

版权所有 中华医学会 中华医学电子音像出版社有限责任公司  京ICP备14006079号-1  网络出版服务许可证：(署)网出证(京)字第075号