角膜内皮细胞相关基础及临床研究的现状
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摘要
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。
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.
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.
引文
[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-?azarczyk 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,Schl?tzer-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.
[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-?azarczyk 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,Schl?tzer-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.