nach oben

Graefe's Archive for Clinical and Experimental Ophthalmology

Erschienen in:

01.07.2015 | Cornea

Mesenchymal stem cells improve healing of the cornea after alkali injury

verfasst von: Diamantis Almaliotis, Georgios Koliakos, Eleni Papakonstantinou, Anastasia Komnenou, Angelos Thomas, Spiros Petrakis, Ilias Nakos, Eleni Gounari, Vasileios Karampatakis

Erschienen in: Graefe's Archive for Clinical and Experimental Ophthalmology | Ausgabe 7/2015

Einloggen, um Zugang zu erhalten

Abstract

Purpose

To evaluate the efficacy of mesenchymal stem cells (MSCs) to ameliorate the consequences of corneal alkali injuries.

Methods

Corneal alkali injuries were created in 30 rabbit eyes. The MSC group (n = 15) were treated with intrastromal and subconjunctival injections of phosphate-buffered saline (PBS) containing 2 × 10⁶ MSCs and topical application. The control group (n = 15) was treated with PBS by the same applications forms. Drops of standard treatment (ascorbate 10 %, citrate 10 %, tobramycin, dexamethasone, Cyclogyl) were instilled for 2 weeks. Rabbits underwent slit-lamp examination, fluorescein staining, photography, and were evaluated for corneal neovascularization, opacification, and epithelial defects. Tear secretion and IOP were also evaluated. Furthermore, the concentration of Serumglutamic–pyruvic transaminase (SGPT) and vascular endothelial factor (VEGF) were measured. Immunohistochemistry was also performed for a-SMA and Ki-67.

Results

Eyes treated with MSCs showed better recovery. The mean neovascularized area was significantly smaller in the MSC group (p < 0.05). A significant difference in the degree of corneal opacification and re-epithelialization was also observed, as well as the IOP at 21 and 28 posttraumatic days (p < 0.05). Histology showed that MSCs resulted in almost normal architecture of eye tissues. After the MSCs infusion, SGPT and VEGF levels in cornea were significantly reduced. Immunohistochemistry demonstrated a reduction of a-SMA in the MSC group with higher mitotic-regenerative activity with the presence of Ki67.

Conclusions

Our study represents a first step in understanding the possibilities of the MSC approach to treatment of alkali injuries of the cornea and shows that such an approach improves clinical outcomes and leads to better prognosis.

Yao L, Li Z-R, Su W-R, Li Y-P, Lin M-L et al (2012) Role of mesenchymal stem cells on cornea wound healing induced by acute alkali burn. PLoS One 7(2):e30842. doi:10.1371/journal.pone.0030842 PubMedCentralPubMedCrossRef

Singh P, Tyagi M, Kumar Y, Gupta KK, Sharma PD (2013) Ocular chemical injuries and their management. Oman J Ophthalmol 6(2):83–86PubMedCentralPubMedCrossRef

Ma Y, Xu Y, Xiao Z, Yang W, Zhang C, Song E, Du Y, Li L (2006) Reconstruction of chemically burned rat corneal surface by bone marrow–derived human mesenchymal stem cells. Stem Cells 24(2):315–321PubMedCrossRef

Kuo IC (2004) Corneal wound healing. Curr Opin Ophthalmol 15:311–315PubMedCrossRef

Adamis AP, Aiello LP, D’Amato RA (1999) Angiogenesis and ophthalmic disease. Angiogenesis 3:9–14PubMedCrossRef

Srinivasan BD (1982) Corneal reepithelialization and anti-inflammatory agents. Trans Am Ophthalmol Soc 80:758–822PubMedCentralPubMed

Wagoner MD (1997) Chemical injuries of the eye: current concepts in pathophysiology and therapy. Surv Ophthalmol 41:275–313PubMedCrossRef

Brodovsky SC, McCarty CA, Snibson G, Loughnan M, Sullivan L et al (2000) Management of alkali burns: an 11-year retrospective review. Ophthalmology 107:1829–1835PubMedCrossRef

Cogan DG (1948) Vascularization of the cornea. Its experimental induction by small lesions and a new theory of its pathogenesis. Trans Am Ophthalmolol Soc 46:457–471

10.

Langham M (1953) Observations on the growth of blood vessels into the cornea; application of a new experimental technique. Br J of Ophthalmol 37(4):210–222CrossRef

11.

Lee P, Wang CC, Adamis AP (1998) Ocular neovascularization: epidemiologic review. Surv Ophthalmol 43:245–269PubMedCrossRef

12.

Lin KJ, Loi MX, Lien GS, Cheng CF, Pao HY, Chang YC, Ji AT, Ho JH (2013) Topical administration of orbital fat-derived stem cells promotes corneal tissue regeneration. Stem Cell Res Therapy 4(3):72CrossRef

13.

Arora R, Mehta D, Jain V (2005) Amniotic membrane transplantation in acute chemical burns. Eye 19(3):273–278PubMedCrossRef

14.

Mitra S (2009) Combined autologous and allograft limbal cell transplantation with penetrating keratoplasty in a case of chemical corneal burn patient. Oman J Ophthalmol 2(3):126–129. doi:10.4103/0974-620X.57312 PubMedCentralPubMedCrossRef

15.

Stamper RL, Lieberman MF, Drake MV (2009) Becker-Shaffer’s Diagnosis and Therapy of the Glaucomas, 8th edn. Mosby-Elsevier, China

16.

Fish R, Davidson RS (2010) Management of ocular thermal and chemical injuries, including amniotic membrane therapy. Curr Opin Ophthalmol 21(4):317–321. doi:10.1097/ICU.0b013e32833a8da2 PubMed

17.

Tuft SJ, Shortt AJ (2009) Surgical rehabilitation following severe ocular burns. Eye Oct 23(10):1966–1971. doi:10.1038/eye.2008.414 CrossRef

18.

Shields MB (1998) Textbook of Glaucoma, 4th edn. Williams & Wilkins, Baltimore, MD

19.

Hemmati H, Colby KA (2012) Treating acute chemical injuries of the cornea. Cornea, Ophthalmic Pearls, pp 43–45

20.

Kosoko A, Vu Q, Kosoko-Lasaki O (2009) Chemical ocular burns: a case review. Am J Clin Med 6(3):41

21.

Crum R, Szabo S, Folkman J (1985) A new class of steroids inhibits angiogenesis in the presence of heparin or a heparin fragment. Science 230:1375–1378PubMedCrossRef

22.

Ambati BK, Joussen AM, Ambati J et al (2002) Angiostatin inhibits and regresses corneal neovascularization. Arch Ophthalmol 120(8):1063–1068PubMedCrossRef

23.

Joussen AM, Kruse FE, Volcker HE, Kirchhof B (1999) Topical application of methotrexate for inhibition of corneal angiogenesis. Graefes Arch Clin Exp Ophthalmol 237(11):920–927PubMedCrossRef

24.

Mendelsohn AD, Stock EL, Lo GG, Schneck GL (1986) Laser photocoagulation of feeder vessels in lipid keratopathy. Ophthalmic Surg 17(8):502–508PubMed

25.

Peyman GA, Kivilcim M, Morales AM et al (2007) Inhibition of corneal angiogenesis by ascorbic acid in the rat model. Graefes Arch Clin Exp Ophthalmol 245(10):1461–1467PubMedCrossRef

26.

Benelli U, Bocci G, Danesi R et al (1998) The heparan sulfate suleparoide inhibits rat corneal angiogenesis and in vitro neovascularization. Exp Eye Res 67(2):133–142PubMedCrossRef

27.

D’Amato RJ, Loughnan MS, Flynn E et al (1994) Thalidomide is an inhibitor of angiogenesis. Proc Natl Acad Sci U S A 91(9):4082–4085PubMedCentralPubMedCrossRef

28.

Ey RC, Hughes WF, Bloome MA et al (1968) Prevention of corneal vascularization. Am J Ophthalmol 66(6):1118–1131PubMedCrossRef

29.

Kvanta A, Sarman S, Fagerholm P, Seregard S, Steen B (2000) Expression of matrix metalloproteinase-2 (MMP-2) and vascular endothelial growth factor (VEGF) in inflammation-associated corneal neovascularization, Exp. Eye Res 70(4):419–428CrossRef

30.

Phillips GD, Stone AM, Jones BD et al (1994) Vascular endothelial growth factor (rhVEGF165) stimulates direct angiogenesis in the rabbit cornea. In Vivo 8(6):961–965PubMed

31.

Philipp W, Speicher L, Humpel C (2000) Expression of vascular endothelial growth factor and its receptors in inflamed and vascularized human corneas. Invest Ophthalmol Vis Sci 41(9):2514–2522PubMed

32.

Oh W, Kim DS, Yang YS, Lee JK (2008) Immunological properties of umbilical cord blood-derived mesenchymal stromal cells. Cell Immunol 251(2):116–123. doi:10.1016/j.cellimm.2008.04.003 PubMedCrossRef

33.

Oh JY, Kim MK, Shin MS, Lee HJ, Ko JH et al (2008) The anti-inflammatory and anti-angiogenic role of mesenchymal stem cells in corneal wound healing following chemical injury. Stem Cell 26(4):1047–1055. doi:10.1634/stemcells.2007-0737 CrossRef

34.

Ye J, Yao K, Kim JC (2006) Mesenchymal stem cell transplantation in a rabbit corneal alkali burn model: engraftment and involvement in wound healing. Eye (Lond) 20(4):482–490CrossRef

35.

Pittenger MF, Mackay AM, Beck SC et al (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284(5411):143–147. doi:10.1126/science.284.5411.143 PubMedCrossRef

36.

Hakuno D, Fukuda K, Makino S et al (2000) Bone marrow-derived regenerated cardiomyocytes (CMG cells) express functional adrenergic and muscarinic receptors. Circulation 105(3):380–386CrossRef

37.

Zannettino AC, Paton S, Arthur A, Khor F, Itescu S et al (2008) Multipotential human adipose-derived stromal stem cells exhibit a perivascular phenotype in vitro and in vivo. J Cell Physiol 214(2):413–421PubMedCrossRef

38.

Hoogduijin MJ, Crop MJ, Peeters AM, Van Osch GJ, Balk AH et al (2007) Human heart, spleen, and perirenal fat-derived mesenchymal stem cells have immunomodulatory capacities. Stem Cells Dev 16(4):597–604CrossRef

39.

Su WR, Zhang QZ, Shi SH, Nguyen AL, Le AD (2011) Human gingiva-derived mesenchymal stromal cells attenuate contact hypersensitivity via prostaglandin E(2)-dependent mechanisms. Stem Cells 29(11):1849–1860. doi:10.1002/stem.738 PubMedCrossRef

40.

Arnalich-Montiel F, Pastor S, Blazquez-Martinez A, Fernandez- Delgado J, Nistal M, Alio JL (2008) Adipose-derived stem cells are a source for cell therapy of the corneal stroma. Stem Cells 26(2):570–579PubMedCrossRef

41.

Karathanasis V, Petrakis S, Topouridou K, Koliakou E, Koliakos G, Demiri E (2013) Intradermal injection of GFP-producing adipose-derived stromal cells promotes survival of random-pattern skin flaps in rats. Eur J Plast Surg 36(5):281–288CrossRef

42.

Jones EA, English A, Kinsey SE, Straszynski L, Emery P, Ponchel F, McGonagle D (2006) Optimization of a flow cytometry-based protocol for detection and phenotypic characterization of multipotent mesenchymal stromal cells from human bone marrow. Cytometry B Clin Cytom 70(6):391–399PubMedCrossRef

43.

Association for Research in Vision and Ophthalmology. Statement for the use of animals in ophthalmic and visual research. (2007) Available at: http://www.arvo.org/eweb/dynamicpage.aspx?siteZarvo2& webcodeZAnimalsResearch

44.

Bagley DM, Casterton PL, Dressler WE et al (2006) Proposed new classification scheme for chemical injury to the human eye. Regul Toxicol Pharmacol 45(2):206–213PubMedCrossRef

45.

Rusanen E, Florin M, Hässig M, Spiess BM (2010) Evaluation of a rebound tonometer (Tonovet) in clinically normal cat eyes. Vet Ophthalmol 13(1):31–36. doi:10.1111/j.1463-5224.2009.00752.x PubMedCrossRef

46.

Leiva M, Naranjo C, Peña MT (2006) Comparison of the rebound tonometer (ICare) to the applanation tonometer (Tonopen XL) in normotensive dogs. Vet Ophthalmol 9(1):17–21PubMedCrossRef

47.

Edward J. Bilsky S. Stevens Negus (2009) Opiate receptors and antagonists: from bench to clinic (Contemporary Neuroscience) pp 263

48.

Jiang D, Hu Y, Ling S (2004) Expression of VEGF-C in rat cornea after alkali injury. J Huazhong Univ Sci Technolog Med Sci 24(5):483–485PubMedCrossRef

49.

Friedenstein AJ, Petrakova KV, Kurolesova AI, Froloba GP (1968) Heterotopic of bone marrow. Analysis of precursor cells for osteogenic and hematopoietic. Transplantation 6(2):230–247PubMedCrossRef

50.

He Q, Wan C, Li G (2007) Concise review: multipotent mesenchymal stromal cells in blood. Stem Cells 25(1):69–77PubMedCrossRef

51.

Polisetty N, Fatima A, Madhira SL, Sangwan VS, Vemuganti GK (2008) Mesenchymal cells from limbal stroma of human eye. Mol Vis 14:431–442PubMedCentralPubMed

52.

Yao L, Bai H (2013) Review: Mesenchymal stem cells and corneal reconstruction. Mol Vis 19:2237–2243PubMedCentralPubMed

53.

Prockop DJ (1997) Marrow stromal cells as stem cells for nonhematopoietic tissue. Science 276(5309):71–74. doi:10.1126/science.276.5309.71 PubMedCrossRef

54.

Le Blanc K, Tammik C, Rosendahl K, Zetterberg E, Ringdén O (2003) HLA expression and immunologic properties of differentiated and undifferentiated mesenchymal stem cells. Exp Hematol 31(10):890–896PubMedCrossRef

55.

Reggiani MG, Marcos L, Pizzolatti WD, Santhiago R, Budel MV, Moreira H (2011) The effect of subconjunctival bevacizumab on corneal neovascularization, inflammation and re-epithelization in a rabbit model. Clinics 66(8):1443–1449CrossRef

56.

Miltiadis P, Panagiotis TG, Vasilios L, Alexandros R, Evaggelos G-B, Ioannis V (2008) Inhibition of corneal neovascularization by subconjunctival bevacizumab in an animal model. Am J Ophthalmol 145(3):424–431. doi:10.1016/j.ajo.2007.11.003 CrossRef

57.

Jiang TS, Cai L, Ji WY, Hui YN, Wang YS et al (2010) Reconstruction of the corneal epithelium with induced marrow mesenchymal stem cells in rats. Mol Vis 16:1304–1316PubMedCentralPubMed

58.

Lan Y, Kodati S, Lee HS, Omoto M, Jin Y, Chauhan SK (2012) Kinetics and function of mesenchymal stem cells in corneal injury. Invest Ophthalmol Vis Sci 53(7):3638–3644. doi:10.1167/iovs.11-9311 PubMedCrossRef

59.

Ho JH, Ma WH, Tseng TC, Chen YF, Chen MH, Lee OK (2011) Isolation and characterization of multi-potent stem cells from human orbital fat tissues. Tissue Eng Part A 17(1–2):255–266. doi:10.1089/ten.TEA.2010.0106 PubMedCrossRef

60.

Agorogiannis GI, Alexaki VI, Castana O, Kymionis GD (2012) Topical application of autologous adipose-derived mesenchymal stem cells (MSCs) for persistent sterile corneal epithelial defect. Graefes Arch Clin Exp Ophthalmol 250(3):455–457. doi:10.1007/s00417-011-1841-3 PubMedCrossRef

61.

Liu K, Chi L, Guo L et al (2008) The interactions between brain microvascular endothelial cells and mesenchymal stem cells under hypoxic conditions. Microvasc Res 75:59–67PubMedCrossRef

62.

Ball SG, Shuttleworth CA, Kielty CM (2007) Mesenchymal stem cells and neovascularization: role of platelet-derived growth factor receptors. J Cell Mol Med 11:1012–1030PubMedCentralPubMedCrossRef

63.

Desmouliere A, Darby IA, Gabbiani G (2003) Normal and pathologic soft tissue remodeling: role of the myofibroblast, with special emphasis on liver and kidney fibrosis. Lab Invest 83:1689–1707PubMedCrossRef

64.

Jester JV, Huang J, Petroll WM, Cavanagh HD (2002) TGFbeta induced myofibroblast differentiation of rabbit keratocytes requires synergistic TGFbeta, PDGF and integrin signaling. Exp Eye Res 75:645–657PubMedCrossRef

65.

Ishizaki M, Wakamatsu K, Matsunami T, Yamanaka N, Saiga T, Shimizu Y et al (1994) Dynamics of the expression of cytoskeleton components and adherens molecules by fibroblastic cells in alkali-burned and lacerated corneas. Exp Eye Res 59(5):537–549PubMedCrossRef

66.

Goto Y, Suzuki K, Ono T, Sasaki M, Toyota T (1988) Development of diabetes in the non-obese NIDDM rat (GK rat). Adv Exp Med Biol 246:29–31PubMedCrossRef

67.

Goto Y (1988) What do spontaneously diabetic animals suggest? (in Japanese) Nippon Naika Gakkai Zasshi 77:1177–1185PubMedCrossRef

68.

Trinkaus-Randall V, Edelhauser HF, Leibowitz HM, et al. (1998) Corneal structure and function. Leibowitz HM Waring GO eds. Corneal Disorders. 2nd ed. 2–31.

69.

Taranta Martin LF, Rocha E, Garcia S, Paula J (2013) Topical Brazilian propolis improves corneal wound healing and inflammation in rats following alkali burns. BMC Complement Altern Med 13:337CrossRef

70.

Zhao M, Chen J, Yang P (2000) Immunologic experimental studies on the alkali burn of cornea in rats] Chinese. Zhonghua Yan Ke Za Zhi 36:40–42. 4PubMed

71.

Sun TT, Green H (1977) Cultured epithelial cells of cornea, conjunctiva and skin: absence of marked intrinsic divergence of their differentiated states. Nature 269:489–493PubMedCrossRef

Titel: Mesenchymal stem cells improve healing of the cornea after alkali injury
verfasst von: Diamantis Almaliotis
Georgios Koliakos
Eleni Papakonstantinou
Anastasia Komnenou
Angelos Thomas
Spiros Petrakis
Ilias Nakos
Eleni Gounari
Vasileios Karampatakis
Publikationsdatum: 01.07.2015
Verlag: Springer Berlin Heidelberg
Erschienen in: Graefe's Archive for Clinical and Experimental Ophthalmology / Ausgabe 7/2015
Print ISSN: 0721-832X
Elektronische ISSN: 1435-702X
DOI: https://doi.org/10.1007/s00417-015-3042-y

Update Augenheilkunde

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

Newsletter bestellen

Springer Medizin

Mesenchymal stem cells improve healing of the cornea after alkali injury

Abstract

Purpose

Methods

Results

Conclusions

Neu im Fachgebiet Augenheilkunde

Ophthalmika in der Schwangerschaft

Operative Therapie und Keimnachweis bei endogener Endophthalmitis

Bakterielle endogene Endophthalmitis

So erreichen Sie eine bestmögliche Wundheilung der Kornea

Update Augenheilkunde

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusions

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 7/2015

Serum and aqueous xanthine oxidase levels, and mRNA expression in anterior lens epithelial cells in pseudoexfoliation

The long-term outcome of the refractive error in children with hypermetropia

Evaluating the long-term efficacy of short-duration 0.1 mg/ml and 0.2 mg/ml MMC in primary trabeculectomy for primary adult glaucoma

Treatment of stage 3 Coats’ disease by endolaser photocoagulation via a two-port pars plana nonvitrectomy approach

Central corneal thickness determination in corneal edema using ultrasound pachymetry, a Scheimpflug camera, and anterior segment OCT

Ophthalmology and the aging society (Essentials in Ophthalmology), Editors: Scholl HPN, Massof RW, West S (2013) ISBN: 978-3-642-36323-8, Springer

Neu im Fachgebiet Augenheilkunde

Ophthalmika in der Schwangerschaft

Operative Therapie und Keimnachweis bei endogener Endophthalmitis

Bakterielle endogene Endophthalmitis

So erreichen Sie eine bestmögliche Wundheilung der Kornea

Update Augenheilkunde