Skip to main content
Hauptrubriken
CME Facharzt-Training Webinare Zeitschriften Bücher e.Medpedia Podcast
Service
Jobbörse Info & Hilfe
Fachgebiete
Anästhesiologie Allgemeinmedizin Arbeitsmedizin Augenheilkunde Chirurgie Dermatologie Gynäkologie und Geburtshilfe HNO Innere Medizin Kardiologie Neurologie Onkologie und Hämatologie Orthopädie und Unfallchirurgie Pädiatrie Pathologie Psychiatrie Radiologie Rechtsmedizin Urologie Zahnmedizin
Themen
Klimawandel und Gesundheit Neues aus dem Markt COVID-19 Praxis und Beruf Seltene Erkrankungen GOÄ & EBM Panorama
Sammlungen
Kasuistiken Algorithmen & Infografiken Blickdiagnosen Arthropedia FlapFinder (für Dermatochirurgen) Videos Kongressberichterstattung Medizin für Apothekerinnen und Apotheker Für Ärztinnen und Ärzte in Weiterbildung Für Medizinstudierende
Erweiterte Suche
Anmelden
nach oben
Advances in Therapy
Erschienen in: Advances in Therapy 3/2020

30.01.2020 | Review

Revisiting Existing Evidence of Corneal Endothelial Progenitors and Their Potential Therapeutic Applications in Corneal Endothelial Dysfunction

verfasst von: Yaa-Jyuhn J. Meir, Hung-Chi Chen, Chien-Chang Chen, Hui-Kang D. Ma

Erschienen in: Advances in Therapy | Ausgabe 3/2020

Einloggen, um Zugang zu erhalten

Abstract

Purpose

A recent successful clinical trial demonstrated that a less invasive cell-injection procedure is a viable medical modality for treating corneal endothelial dystrophy. This medical advance still relies on human corneal endothelial cell (HCEC) sources derived from rare cornea donations. The progenitor of the corneal endothelium, which has the characteristics of active proliferation and lineage restriction, will be an ideal cell source for expansion ex vivo. However, the distribution of progenitor-like cells in the corneal endothelial sheet has been under debate for more than a decade.

Methods

This paper re-examines the scientific evidence of the existence of human corneal endothelial progenitors (HCEPs) from the aspects of (1) the origin of cornea formation during ocular development, (2) manifestations from clinical studies, and (3) the distinctive properties of ex vivo-cultured subpopulations.

Results

The discrepancies regarding different types of progenitor-like cells in various locations of the cornea are based on the fact that the corneal endothelium is derived from different cell types with multiple origins during corneal formation.

Conclusions

Resolving this long-standing issue in corneal biology will enable various types of progenitors to be isolated and their potencies regarding the formation of functional endothelial cells to be examined. Additionally, an effective niche system for quantitatively producing therapeutic cells can be formulated to satisfy the burning need associated with corneal endothelial dystrophy in the future.
Literatur
1.
Gain P, Remy J, He Z, et al. Global survey of corneal transplantation and eye banking. JAMA Ophthalmol. 2016;134(2):167–73.PubMed
2.
Price MO, Price FW. Endothelial keratoplasty review. Clin Exp Ophthalmol. 2010;38(2):128–40.PubMed
3.
Koizumi N, Okumura N, Kinoshita S. Development of new therapeutic modalities for corneal endothelial disease focused on the proliferation of corneal endothelial cells using animal models. Exp Eye Res. 2012;95(1):60–7.PubMed
4.
Kinoshita S, Koizumi N, Ueno M, et al. Injection of cultured cells with a ROCK inhibitor for bullous keratopathy. NEJM. 2018;378(11):995–1003.PubMed
5.
Chen S, Zhu Q, Sun H, et al. Advances in culture, expansion and mechanistic studies of corneal endothelial cells: a systematic review. J Biomed Sci. 2019;26:2.PubMedPubMedCentral
6.
Yokoo S, Yamagami S, Yanagi Y, et al. Human corneal endothelial cell precursors isolated by sphere-forming assay. Invest Ophthalmol Vis Sci. 2005;46:1626–31.PubMed
7.
Yamagami S, Yokoo S, Mimura T, et al. Distribution of precursors in human corneal stromal cells and endothelial cells. Ophthalmology. 2007;114:433–9.PubMed
8.
Hirata-Tominaga K, Nakamura T, Okumura N, et al. Corneal endothelial cell fate is maintained by LGR5 through the regulation of hedgehog and Wnt pathway. Stem Cells. 2013;31(7):1396–407.PubMed
9.
Hara S, Hayashi R, Soma T, et al. Identification and potential application of human corneal endothelial progenitor cells. Stem Cells Dev. 2014;23:2190–201.PubMed
10.
Katikireddy KR, Schmedt T, Price MO, Price FW, Jurkunas UV. Existence of neural crest-derived progenitor cells in normal and Fuchs endothelial dystrophy corneal endothelium. Am J Pathol. 2016;186(10):2736–50.PubMedPubMedCentral
11.
McCabe KL, Lanza R. Corneal replacement tissue. In: Lanza R, Langer R, Vacanti J, editors. Principles of tissue engineering. Amsterdam: Elsevier; 2014; pp. 1413–1425.
12.
Barry PA, Petroll WM, Andrews PM, Cavanagh HD, Jester JV. The spatial organization of corneal endothelial cytoskeletal proteins and their relationship to the apical junctional complex. Invest Ophthalmol Vis Sci. 1995;36(6):1115–24.PubMed
13.
14.
Joyce N. Proliferative capacity of corneal endothelial cells. Exp Eye Res. 2012;95(1):16–23.PubMed
15.
Senoo T, Joyce NC. Cell cycle kinetics in corneal endothelium from old and young donors. Invest Ophthalmol Vis Sci. 2000;41(3):660–7.PubMed
16.
Yoshida K, Kase S, Nakayama K, et al. Involvement of p27 KIP1 in the proliferation of the developing corneal endothelium. Invest Ophthalmol Vis Sci. 2004;45(7):2163.PubMed
17.
Joyce NC, Meklir B, Joyce SJ, Zieske JD. Cell cycle protein expression and proliferative status in human corneal cells. Invest Ophthalmol Vis Sci. 1996;37:645–55.PubMed
18.
Marsuda M, Sawa M, Edelhauser HF, Stephen PB, Neufeld AH, Kenyon KR. Cellular migration and morphology in corneal endothelial wound repair. Invest Ophthalmol Vis Sci. 1985;26(4):443–9.
19.
Sherrard ES. The corneal endothelium in vivo: its response to mild trauma. Exp Eye Res. 1976;22(4):347–57.PubMed
20.
Murphy C, Alvarado J, Juster R, Maglio M. Prenatal and postnatal cellularity of the human corneal endothelium. A quantitative histologic study. Invest Ophthalmol Vis Sci. 1984;25(3):312–22.PubMed
21.
Bourne WM, Nelson LIL, Hodge DO. Central corneal endothelial cell changes over a ten-year period. Invest Ophthalmol Vis Sci. 1997;38(3):779–82.PubMed
22.
Kim KW, Park SH, Lee SJ, Kim JC. Ribonuclease 5 facilitates corneal endothelial wound healing via activation of PI3-kinase/Akt pathway. Sci Rep. 2016;6:31162.PubMedPubMedCentral
23.
McGowan SL, Edelhauser HF, Pfister RR, Whikehart DR. Stem cell markers in the human posterior limbus and corneal endothelium of unwounded and wounded corneas. Mol Vis. 2007;13:1984–2000.PubMed
24.
Konomi K, Zhu C, Harris D, Joyce NC. Comparison of the proliferative capacity of human corneal endothelial cells from the central and peripheral areas. Invest Ophthalmol Vis Sci. 2005;46:4086–91.PubMed
25.
Mimura T, Joyce NC. Replication competence and senescence in central and peripheral human corneal endothelium. Invest Ophthalmol Vis Sci. 2006;47:1387–96.PubMed
26.
Bednarz J, Richard G, Bohnke M, Engelmann K. Differences in proliferation and migration of corneal endothelial cells after cell transplantation in vitro. Ger J Ophthalmol. 1996;5:346–51.PubMed
27.
Zhu C, Joyce NC. Proliferative response of corneal endothelial cells from young and older donors. Invest Ophthalmol Vis Sci. 2004;45:1743–51.PubMed
28.
Okumura N, Kay EP, Nakahara M, et al. Inhibition of TGF-beta signaling enables human corneal endothelial cell expansion in vitro for use in regenerative medicine. PLoS One. 2013;8:e58000.PubMedPubMedCentral
29.
Peh GS, Beuerman RW, Colman A, et al. Human corneal endothelial cell expansion for corneal endothelium transplantation: an overview. Transplantation. 2011;91:811–9.PubMed
30.
Hamuro J, Ueno M, Toda M, Sotozono C, Montoya M, Kinoshita S. Cultured human corneal endothelial cell aneuploidy dependence on the presence of heterogeneous subpopulations with distinct differentiation phenotypes. Invest Ophthalmol Vis Sci. 2016;57(10):4385–92.PubMed
31.
Hamuro J, Toda M, Asada K, et al. Cell Homogeneity indispensable for regenerative medicine by cultured human corneal endothelial cells. Invest Ophthalmol Vis Sci. 2016;57(11):4749–61.PubMed
32.
Cheong YK, Ngoh ZX, Peh GS, et al. Identification of cell surface markers glypican-4 and CD200 that differentiate human corneal endothelium from stromal fibroblasts. Invest Ophthalmol Vis Sci. 2013;54:4538–47.PubMed
33.
Toda M, Ueno M, Hiraga A, et al. Production of homogeneous cultured human corneal endothelial cells indispensable for innovative cell therapy. Invest Ophthalmol Vis Sci. 2017;58:2011–20.PubMed
34.
Okumura N, Hirano H, Numata R, et al. Cell surface markers of functional phenotypical corneal endothelial cells. Invest Ophthalmol Vis Sci. 2014;55(11):7610–8.PubMed
35.
Hamuro J, Ueno M, Asada K, et al. Metabolic plasticity in cell state homeostasis and differentiation of cultured human corneal endothelial cells. Invest Ophthalmol Vis Sci. 2016;57(10):4452–63.PubMed
36.
Ueno M, Asada K, Toda M, et al. MicroRNA profiles qualify phenotypic features of cultured human corneal endothelial cells. Invest Ophthalmol Vis Sci. 2016;57(13):5509–17.PubMed
37.
Pei YF, Rhodin JAG. The prenatal development of the mouse eye. Anat Rec. 1970;168:105–26.PubMed
38.
Dublin I. Comparative embryologic studies of the early development of the cornea and the pupillary membrane in reptiles, birds, and mammals. Acta Anat (Basel). 1970;76:381–408.
39.
Kidson SH, Kume T, Deng K, Winfrey V, Hogan BL. The forkhead/winged-helix gene, Mf1, is necessary for the normal development of the cornea and formation of the anterior chamber in the mouse eye. Dev Biol. 1999;211:306–22.PubMed
40.
Reneker LW, Silversides DW, Xu L, Overbeek PA. Formation of corneal endothelium is essential for anterior segment development. Development. 2000;127:533–42.PubMed
41.
Flugel-Koch C, Ohlmann A, Piatigorsky J, Tamm ER. Overexpression of TGF-b1 alters early development of cornea and lens in transgenic mice. Dev Dyn. 2002;225:111–25.PubMed
42.
Wulle KG. The development of the productive and draining system of the aqueous humor in the human eye. Adv Ophthalmol. 1972;26:269–355.
43.
Smith RS, Zabaleta A, Savinova OV, John SW. The mouse anterior chamber angle and trabecular meshwork develop without cell death. BMC Dev Biol. 2001;1:3.PubMedPubMedCentral
44.
Reme C, d’Epinay SL. Periods of development of the normal human chamber angle. Doc Ophthalmol. 1981;51:241–68.PubMed
45.
Johnston MC, Noden DM, Hazelton RD, Coulombre JL, Coulombre AJ. Origins of avian ocular and periocular tissues. Exp Eye Res. 1979;29:27–43.PubMed
46.
Trainor PA, Tam PP. Cranial paraxial mesoderm and neural crest cells of the mouse embryo: co-distribution in the craniofacial mesenchyme but distinct segregation in branchial arches. Development. 1995;121:2569–82.PubMed
47.
Hay ED. Development of the vertebrate cornea. Int Rev Cytol. 1980;63:263–322.PubMed
48.
Duke-Elder S, Cook C. Part 1. Embryology (System of Ophthalmology, Vol. III). In: Duke-Elder S, editor. Normal and abnormal development. London: Springer; 1963.
49.
Raviola G. Schwalbe line’s cells: a new cell type in the trabecular meshwork of Macaca mulatta. Invest Ophthalmol Vis Sci. 1982;22:45–56.PubMed
50.
Schimmelpfennig BH. Direct and indirect determination of nonuniform cell density distribution in human corneal endothelium. Invest Ophthalmol Vis Sci. 1984;25:223–9.PubMed
51.
Daus W, Volcker HE, Meysen H, et al. Vital staining of the corneal endothelium–increased possibilities of diagnosis. Fortschr Ophthalmol. 1989;86:259–64.PubMed
52.
Amann J, Holley GP, Lee SB, et al. Increased endothelial cell density in the paracentral and peripheral regions of the human cornea. Am J Ophthalmol. 2003;135:584–90.PubMed
53.
He Z, Campolmi N, Gain P, et al. Revisited microanatomy of the corneal endothelial periphery: new evidence for continuous centripetal migration of endothelial cells in humans. Stem Cells. 2012;30:2523–34.PubMed
54.
55.
Whikehart DR, Parikh CH, Vaughn AV, Mishler K, Edelhauser HF. Evidence suggesting the existence of stem cells for the human corneal endothelium. Mol Vis. 2005;11:816–24.PubMed
56.
Zhang Y, Cai S, Tseng SCG, Zhu YT. Isolation and expansion of multipotent progenitors for human trabecular meshwork. Sci Rep. 2018;8:2814.PubMedPubMedCentral
57.
Zhu Q, Zhang Y, Tighe S, Liu Y, Zhu Y, Hu M. Human trabecular meshwork progenitor. Int J Med Sci. 2019;16:704–10.PubMedPubMedCentral
58.
Joyce NC, Harris DL, Mello DM. Mechanisms of mitotic inhibition in corneal endothelium: contact inhibition and TGF-beta2. Invest Ophthalmol Vis Sci. 2002;43:2152–9.PubMed
59.
Joyce NC, Zhu CC, Harris DL. Relationship among oxidative stress, DNA damage, and proliferative capacity in human corneal endothelium. Invest Ophthalmol Vis Sci. 2009;50:2116–22.PubMed
60.
Konomi K, Joyce NC. Age and topographical comparison of telomere lengths in human corneal endothelial cells. Mol Vis. 2007;13:1251–8.PubMed
61.
Xiao X, Wang Y, Gong H, et al. Molecular evidence of senescence in corneal endothelial cells of senescence-accelerated mice. Mol Vis. 2009;15:747–61.PubMedPubMedCentral
62.
Wollensak G, Green WR. Analysis of sex-mismatched human corneal transplants by fluorescence in situ hybridization of the sex-chromosomes. Exp Eye Res. 1999;68:341–6.PubMed
63.
Lagali NS, Stenevi U, Claesson M, et al. Donor and recipient endothelial cell population of the transplanted human cornea: a two-dimensional imaging study. Invest Ophthalmol Vis Sci. 2010;51:1898–904.PubMed
64.
Arbelaez JG, Price MO, Price FW Jr. Long-term follow-up and complications of stripping Descemet membrane without placement of graft in eyes with Fuchs endothelial dystrophy. Cornea. 2014;33(12):1295–9.PubMed
65.
Balachandran C, Ham L, Verschoor CA, Ong TS, van der Wees J, Melles GR. Spontaneous corneal clearance despite graft detachment in Descemet membrane endothelial keratoplasty. Am J Ophthalmol. 2009;148(227–234):e1.
66.
Baydoun L, Ham L, Borderie V, et al. Endothelial survival after Descemet membrane endothelial keratoplasty: effect of surgical indication and graft adherence status. JAMA Ophthalmol. 2015;133:1277–85.PubMed
67.
Van den Bogerd B, Dhubhghaill SN, Koppen C, Tassignon MJ, Zakaria N. A review of the evidence for in vivo corneal endothelial regeneration. Surv Ophthalmol. 2018;63:149–65.PubMed
68.
Okumura N, Koizumi N, Kay EP, et al. The ROCK inhibitor eye drop accelerates corneal endothelium wound healing. Invest Ophthalmol Vis Sci. 2013;54:2493–502.PubMed
69.
Borkar DS, Veldman P, Colby KA. Treatment of Fuchs endothelial dystrophy by Descemet stripping without endothelial keratoplasty. Cornea. 2016;35:1267–73.PubMed
70.
Melles GR, Ong TS, Ververs B, van der Wees J. Preliminary clinical results of Descemet membrane endothelial keratoplasty. Am J Ophthalmol. 2008;145:222–7.PubMed
71.
Price MO, Giebel AW, Fairchild KM, Price FW Jr. Descemet’s membrane endothelial keratoplasty: prospective multicenter study of visual and refractive outcomes and endothelial survival. Ophthalmology. 2009;116:2361–8.PubMed
72.
Tan DT, Dart JK, Holland EJ, Kinoshita S. Corneal transplantation. Lancet. 2012;379:1749–61.PubMed
73.
Schlögl A, Tourtas T, Kruse FE, Weller JM. Long-term clinical outcome after Descemet membrane endothelial keratoplasty. Am J Ophthalmol. 2016;169:218–26.PubMed
74.
Wacker K, Baratz KH, Maguire LJ, McLaren JW, Patel SV. Descemet stripping endothelial keratoplasty for Fuchs’ endothelial corneal dystrophy: five-year results of a prospective study. Ophthalmology. 2016;123:154–60.PubMed
75.
Croze RH, Buchholz DE, Radeke MJ, et al. ROCK inhibition extends passage of pluripotent stem cell-derived retinal pigmented epithelium. Stem Cells Transl Med. 2014;3:1066–78.PubMedPubMedCentral
76.
77.
Yoshihara M, Ohmiya H, Hara S, et al. Discovery of molecular markers to discriminate corneal endothelial cells in the human body. PLoS One. 2015;10(3):e0117581.PubMedPubMedCentral
78.
Yoshihara M, Hara S, Tsujikawa M, et al. Restricted presence of POU6F2 in human corneal endothelial cells uncovered by extension of the promoter-level expression atlas. EBioMedicine. 2017;25:175–86.PubMedPubMedCentral
79.
80.
Soh YQ, Peh GSL, Mehta JS. Translation issues for human corneal endothelial tissue engineering. J Tissue Eng Regen Med. 2017;11(9):2425–42.PubMed
81.
82.
Chen Y, Huang K, Nakatsu MN, Xue Z, Deng SX, Fan G. Identification of novel molecular markers through transcriptomic analysis in human fetal and adult corneal endothelial cells. Hum Mol Genet. 2013;22:1271–9.PubMed
83.
Ding V, Chin A, Peh G, Mehta JS, Choo A. Generation of novel monoclonal antibodies for the enrichment and characterization of human corneal endothelial cells (hCENC) necessary for the treatment of corneal endothelial blindness. MAbs. 2014;6(6):1439–52.PubMedPubMedCentral
Metadaten
Titel
Revisiting Existing Evidence of Corneal Endothelial Progenitors and Their Potential Therapeutic Applications in Corneal Endothelial Dysfunction
verfasst von
Yaa-Jyuhn J. Meir
Hung-Chi Chen
Chien-Chang Chen
Hui-Kang D. Ma
Publikationsdatum
30.01.2020
Verlag
Springer Healthcare
Erschienen in
Advances in Therapy / Ausgabe 3/2020
Print ISSN: 0741-238X
Elektronische ISSN: 1865-8652
DOI
https://doi.org/10.1007/s12325-020-01237-w

Weitere Artikel der Ausgabe 3/2020

Advances in Therapy 3/2020 Zur Ausgabe

Study Protocol

Design and Rationale of a Scandinavian Multicenter Randomized Study Evaluating if Once-Daily Tacrolimus Versus Twice-Daily Cyclosporine Reduces the 3-year Incidence of Chronic Lung Allograft Dysfunction After Lung Transplantation (ScanCLAD Study)

Review

Real-World Data and Randomised Controlled Trials: The Salford Lung Study

Original Research

Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), and Outcomes with Nivolumab in Pretreated Non-Small Cell Lung Cancer (NSCLC): A Large Retrospective Multicenter Study

Original Research

Efficacy and Safety of Intravitreal Aflibercept Treat-and-Extend Regimens in Exudative Age-Related Macular Degeneration: 52- and 96-Week Findings from ALTAIR

Original Research

Evaluating the Effect of Standard of Care Treatment on Burden of Chronic Hepatitis B: A Retrospective Analysis of the United States Veterans Population

Original Research

Long-Term, Real-World Safety and Efficacy of Teneligliptin: A Post-Marketing Surveillance of More Than 10,000 Patients with Type 2 Diabetes in Japan

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

25.04.2024 Allergien und Intoleranzreaktionen Nachrichten

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen
Bildnachweise