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Published in: Graefe's Archive for Clinical and Experimental Ophthalmology 7/2015

01-07-2015 | Cornea

Mesenchymal stem cells improve healing of the cornea after alkali injury

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

Published in: Graefe's Archive for Clinical and Experimental Ophthalmology | Issue 7/2015

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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.
Literature
3.
go back to reference 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 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
5.
go back to reference Adamis AP, Aiello LP, D’Amato RA (1999) Angiogenesis and ophthalmic disease. Angiogenesis 3:9–14PubMedCrossRef Adamis AP, Aiello LP, D’Amato RA (1999) Angiogenesis and ophthalmic disease. Angiogenesis 3:9–14PubMedCrossRef
6.
7.
go back to reference Wagoner MD (1997) Chemical injuries of the eye: current concepts in pathophysiology and therapy. Surv Ophthalmol 41:275–313PubMedCrossRef Wagoner MD (1997) Chemical injuries of the eye: current concepts in pathophysiology and therapy. Surv Ophthalmol 41:275–313PubMedCrossRef
8.
go back to reference 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 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
9.
go back to reference 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 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.
go back to reference 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 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.
go back to reference Lee P, Wang CC, Adamis AP (1998) Ocular neovascularization: epidemiologic review. Surv Ophthalmol 43:245–269PubMedCrossRef Lee P, Wang CC, Adamis AP (1998) Ocular neovascularization: epidemiologic review. Surv Ophthalmol 43:245–269PubMedCrossRef
12.
go back to reference 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 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.
go back to reference Arora R, Mehta D, Jain V (2005) Amniotic membrane transplantation in acute chemical burns. Eye 19(3):273–278PubMedCrossRef Arora R, Mehta D, Jain V (2005) Amniotic membrane transplantation in acute chemical burns. Eye 19(3):273–278PubMedCrossRef
15.
go back to reference Stamper RL, Lieberman MF, Drake MV (2009) Becker-Shaffer’s Diagnosis and Therapy of the Glaucomas, 8th edn. Mosby-Elsevier, China Stamper RL, Lieberman MF, Drake MV (2009) Becker-Shaffer’s Diagnosis and Therapy of the Glaucomas, 8th edn. Mosby-Elsevier, China
18.
go back to reference Shields MB (1998) Textbook of Glaucoma, 4th edn. Williams & Wilkins, Baltimore, MD Shields MB (1998) Textbook of Glaucoma, 4th edn. Williams & Wilkins, Baltimore, MD
19.
go back to reference Hemmati H, Colby KA (2012) Treating acute chemical injuries of the cornea. Cornea, Ophthalmic Pearls, pp 43–45 Hemmati H, Colby KA (2012) Treating acute chemical injuries of the cornea. Cornea, Ophthalmic Pearls, pp 43–45
20.
go back to reference Kosoko A, Vu Q, Kosoko-Lasaki O (2009) Chemical ocular burns: a case review. Am J Clin Med 6(3):41 Kosoko A, Vu Q, Kosoko-Lasaki O (2009) Chemical ocular burns: a case review. Am J Clin Med 6(3):41
21.
go back to reference 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 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.
go back to reference Ambati BK, Joussen AM, Ambati J et al (2002) Angiostatin inhibits and regresses corneal neovascularization. Arch Ophthalmol 120(8):1063–1068PubMedCrossRef Ambati BK, Joussen AM, Ambati J et al (2002) Angiostatin inhibits and regresses corneal neovascularization. Arch Ophthalmol 120(8):1063–1068PubMedCrossRef
23.
go back to reference 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 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.
go back to reference Mendelsohn AD, Stock EL, Lo GG, Schneck GL (1986) Laser photocoagulation of feeder vessels in lipid keratopathy. Ophthalmic Surg 17(8):502–508PubMed Mendelsohn AD, Stock EL, Lo GG, Schneck GL (1986) Laser photocoagulation of feeder vessels in lipid keratopathy. Ophthalmic Surg 17(8):502–508PubMed
25.
go back to reference 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 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.
go back to reference 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 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
28.
go back to reference Ey RC, Hughes WF, Bloome MA et al (1968) Prevention of corneal vascularization. Am J Ophthalmol 66(6):1118–1131PubMedCrossRef Ey RC, Hughes WF, Bloome MA et al (1968) Prevention of corneal vascularization. Am J Ophthalmol 66(6):1118–1131PubMedCrossRef
29.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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
33.
go back to reference 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 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.
go back to reference 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 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
36.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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
44.
go back to reference 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 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
46.
go back to reference 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 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.
go back to reference Edward J. Bilsky S. Stevens Negus (2009) Opiate receptors and antagonists: from bench to clinic (Contemporary Neuroscience) pp 263 Edward J. Bilsky S. Stevens Negus (2009) Opiate receptors and antagonists: from bench to clinic (Contemporary Neuroscience) pp 263
48.
go back to reference 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 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.
go back to reference 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 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.
go back to reference He Q, Wan C, Li G (2007) Concise review: multipotent mesenchymal stromal cells in blood. Stem Cells 25(1):69–77PubMedCrossRef He Q, Wan C, Li G (2007) Concise review: multipotent mesenchymal stromal cells in blood. Stem Cells 25(1):69–77PubMedCrossRef
51.
go back to reference Polisetty N, Fatima A, Madhira SL, Sangwan VS, Vemuganti GK (2008) Mesenchymal cells from limbal stroma of human eye. Mol Vis 14:431–442PubMedCentralPubMed Polisetty N, Fatima A, Madhira SL, Sangwan VS, Vemuganti GK (2008) Mesenchymal cells from limbal stroma of human eye. Mol Vis 14:431–442PubMedCentralPubMed
54.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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
60.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference Goto Y (1988) What do spontaneously diabetic animals suggest? (in Japanese) Nippon Naika Gakkai Zasshi 77:1177–1185PubMedCrossRef Goto Y (1988) What do spontaneously diabetic animals suggest? (in Japanese) Nippon Naika Gakkai Zasshi 77:1177–1185PubMedCrossRef
68.
go back to reference 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. 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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
Metadata
Title
Mesenchymal stem cells improve healing of the cornea after alkali injury
Authors
Diamantis Almaliotis
Georgios Koliakos
Eleni Papakonstantinou
Anastasia Komnenou
Angelos Thomas
Spiros Petrakis
Ilias Nakos
Eleni Gounari
Vasileios Karampatakis
Publication date
01-07-2015
Publisher
Springer Berlin Heidelberg
Published in
Graefe's Archive for Clinical and Experimental Ophthalmology / Issue 7/2015
Print ISSN: 0721-832X
Electronic ISSN: 1435-702X
DOI
https://doi.org/10.1007/s00417-015-3042-y

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