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fbtwitterlinkedinvimeoflicker grey 14rssslideshare1
Carrington, Louise Mary; Albon, Julie; Anderson, Ian; Kamma-Lorger, Christina S.; Boulton, Michael Edwin (2006)
Publisher: Association for Research in Vision and Ophthalmology
Languages: English
Types: Article
Subjects:
PURPOSE: Inhibition of TGF-beta reduces myofibroblast differentiation and fibrosis in the cornea. Determining the actions of distinct TGF-beta isoforms and their inhibitors during early corneal wound healing is an essential step in guiding therapeutic intervention. METHODS: Bovine serum-free corneal cell and wounded organ cultures were challenged with a range of concentrations of TGF-beta1, -beta2, and -beta3; IL-10; and neutralizing human monoclonal antibodies (mAbs) against TGF-beta1 (CAT-192) or -beta2, (CAT-152). Cultures were assessed for re-epithelialization, proliferation (cell counts and cresyl violet assay), morphology (histologic examination), repopulation of the area under the wound, and myofibroblast transformation (alpha-smooth muscle actin) between 0 and 5 days. RESULTS: TGF-beta1 delayed re-epithelialization, increased repopulation of the stroma, increased keratocyte proliferation and was the only isoform to promote myofibroblast differentiation. The anti-TGF-beta1 mAb, CAT-192 promoted re-epithelialization and reduced repopulation of the stroma. Exogenous TGF-beta3 had little effect on re-epithelialization but reduced repopulation of the stroma. IL-10 promoted corneal re-epithelialization at low doses but inhibited this response at high doses. Stromal repopulation was prevented by all doses of IL-10. TGF-beta2 or the anti-TGF-beta2 mAb, CAT-152 had little effect on any repair parameter. CONCLUSIONS: The results confirm TGF-beta1 as the principal isoform in corneal wound healing and suggest that inhibition of the action of TGF-beta1 can promote corneal wound healing. Treatment with the anti-TGF-beta1 mAb CAT-192 accelerates corneal re-epithelialization but reduces cell repopulation of the stroma. The cytokines TGF-beta3 and IL-10 have opposing actions to that of TGF-beta1.
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    • 1. O'Kane S, Ferguson M. Transforming growth factor betas and wound healing. Int J Biochem Cell Biol. 1997;29:63-78.
    • 2. Møller-Pedersen T, Cavanagh H, Petroll W, Jester J. Neutralising antibody to TGF-beta modulates stromal fibrosis but not regression of photoablative effect following PRK. Curr Eye Res. 1998;17: 736 -747.
    • 3. Jester JV, BarryLane PA, Petroll WM, Olsen DR, Cavanagh HD. Inhibition of corneal fibrosis by topical application of blocking antibodies to TGF(beta) in the rabbit. Cornea. 1997;16:177-187.
    • 4. Nishida K, Kinoshita S, Yokoi N, et al. Immunohistochemical localization of transforming growth factor-beta-1, factor-beta-2, and factor-beta-3 latency-associated peptide in human cornea. Invest Ophthalmol Vis Sci. 1994;35:3289 -3294.
    • 5. Nishida K, Sotozono C, Adachi W, Yamamoto S, Yokoi N, Kinoshita S. Transforming growth factor 1, - 2 and - 3 mRNA expression in human cornea. Curr Eye Res. 1995;14:235-241.
    • 6. Pasquale LR, Dorman-Pease ME, Lutty GA, et al. Immunolocalization of Tgf-beta-1, Tgf-beta-2, and Tgf-beta-3 in the anterior segment of the human eye. Invest Ophthalmol Vis Sci. 1993;34:23- 30.
    • 7. Abrahamian A, Xi MS, Donnelly JJ, Rockey JH. Effect of interferongamma on the expression of transforming growth-factor-beta by human corneal fibroblasts: role in corneal immunoseclusion J Interferon Cytokine Res. 1995;15:323-330.
    • 8. Chen KH, Harris DL, Joyce NC. TGF-beta 2 in aqueous humor suppresses S-phase entry in cultured corneal endothelial cells. Invest Ophthalmol Vis Sci. 1999;40:2513-2519.
    • 9. Gupta A, Monroy D, Ji Z, Yoshino K, Huang A, Pflugfelder S. Transforming growth factor beta-1 and beta-2 in human tear fluid. Curr Eye Res. 1996;15:605- 614.
    • 10. Chen C, Michelini-Norris B, Stevens S, et al. Measurement of mRNAs for TGF beta and extracellular matrix proteins in corneas of rats after PRK. Invest Ophthalmol Vis Sci. 2000;41:4108 - 4116.
    • 11. Joyce N, Zieske J. Transforming growth factor beta-receptor expression in the human cornea. Invest Ophthalmol Vis Sci. 1997; 38:1922-1928.
    • 12. Obata H, Kaburaki T, Kato M, Yamashita H. Expression of TGF-beta type I and type II receptors in rat eyes. Curr Eye Res. 1996;15:335-340.
    • 13. Obata H, Kaji Y, Yamada H, Kato M, Tsuru T, Yamashita H. Expression of transforming growth factor-beta superfamily receptors in rat eyes. Acta Ophthalmol Scand. 1999;77:151-156.
    • 14. Wilson S, He Y, Lloyd S. EGF, EGF receptor, basic FGF, TGF beta-1, and IL-1 alpha mRNA in human corneal epithelial cells and stromal fibroblasts. Invest Ophthalmol Vis Sci. 1992;33:1756 -1765.
    • 15. Hayashi GF, Wolf G, Kenyon K. Expression of transforming growth factor-beta in wound healing of vitamin A-deficient rat corneas. Invest Ophthalmol Vis Sci. 1989;30:239 -247.
    • 16. Mita T, Yamashita H, Kaji Y, et al. Effects of transforming growth factor beta on corneal epithelial and stromal function in a rat wound healing model. Graefes Arch Clin Exp Ophthalmol 1998 236:834 - 843.
    • 17. Strissell K, Rinehart W, Fini M. A corneal epithelial inhibitor of stromal cell collagenase synthesis identified as TGF 2. Invest Ophthalmol Vis Sci. 1995;36:151-162.
    • 18. Pancholi S, Tullo A, Khaliq A, Foreman D, Boulton M. The effects of growth factors and conditioned media on the proliferation of human corneal epithelial cells and keratocytes. Graefes Arch Clin Exp Ophthalmol. 1998;235:1- 8.
    • 19. Kaji Y, Mita T, Obata H, et al. Expression of transforming growth factor beta superfamily and their receptors in the corneal stromal wound healing process after excimer laser keratectomy. Br J Ophthalmol. 1998;82:462- 463.
    • 20. Carrington L, Boulton M. HGF and KGF regulate both epithelial and stromal corneal wound healing. J Cataract Refract Surg. 2005;31:412- 423.
    • 21. Foreman D, Pancholi D, Jarvis-Evans J, McLeod D, Boulton M. A simple organ culture model for assessing the effects of growth factors on corneal reepithelialisation. Exp Eye Res. 1996;62:555- 564.
    • 22. Jester J, Barry P, Cavanagh M, Petroll W. Induction of alpha smooth muscle actin expression and myofibroblast transformation in cultured corneal keratocytes. Cornea. 1996;115:505-516.
    • 23. Mita T, Yamashita H, Kaji Y, et al. Functional difference of TGFbeta isoforms regulating corneal wound healing after excimer laser keratectomy. Exp Eye Res. 1999;68:513-519.
    • 24. Blom IE, van Dijk AJ, Wieten L, et al. In vitro evidence for differential involvement of CTGF, TGF beta, and PDGF-BB in mesangial response to injury. Nephrol Dialysis Transplant. 2001;16:1139 - 1148.
    • 25. Shah M, Foreman D, Ferguson M. Neutralisation of TGF-beta 1 and TGF-beta 2 or exogenous addition of TGF-beta 3 to cutaneous rat wounds reduces scarring. J Cell Sci. 1995;108:985-1002.
    • 26. Cowin AJ, Holmes TM, Brosnan P, Ferguson MW. Expression of TGF-beta and its receptors in murine fetal and adult dermal wounds. Eur J Dermatol. 2001;11:424 - 431.
    • 27. Fiorentino DF, Bond MW, Mosmann TR. Two types of mouse T helper cell IV Th2 clones secrete a factor that inhibits cytokine production by Th1 clones. J Exp Med. 1989;170:2081-2095.
    • 28. Serot JM, Bene MC, Foliguet B, Faure GC. Monocyte-derived IL-10- secreting dendritic cells in choroid plexus epithelium. J Neuroimmunol. 2000;105:115-119.
    • 29. Sotozono C, He JC, Matsumoto Y, Kita M, Imanishi J, Kinoshita S. Cytokine expression in the alkali-burned cornea. Curr Eye Res. 1997;16:670 - 676.
    • 30. King WJ, Comer RM, Hudde T, Larkin DF, George AJ. Cytokine and chemokine expression kinetics after corneal transplantation. Transplantation. 2000;70:1225-1233.
    • 31. Enk AH, Katz SI. Identification and induction of keratinocytederived Il-10. J Immunol. 1992;149:92-95.
    • 32. Dosanjh A, Morris RE, Wan B. Bronchial epithelial cell-derived cytokine IL-10 and lung fibroblast proliferation. Transplant Proc. 2001;33:352-354.
    • 33. Yoshida M, Takeuchi M, Streilein JW, et al. Participation of pigment epithelium of iris and ciliary body in ocular immune privilege. 1. Inhibition of T-cell activation in vitro by direct cell-to-cell contact. Invest Ophthalmol Vis Sci. 2000;41:811- 821.
    • 34. Tumpey TM, Cheng H, Yan XT, Oakes JE, Lausch RN. Chemokine synthesis in the HSV-1-infected cornea and its suppression by interleukin-l0. J Leukocyte Biol. 1998;63:486 - 492.
    • 35. Boorstein SM, Elner SG, Meyer RF, et al. Interleukin-10 Inhibition of HLA-DR expression in human herpes stromal keratitis. Ophthalmology. 1994;101:1529 -1535.
    • 36. Minagawa H, Sakai Y, Li Y, Ishibashi T, Inomata H, Mori R. Suppression of infectious virus spread and corneal opacification by the combined use of recombinant interferon beta and interleukin-10 following corneal infection with herpes simplex virus-1 in mice. Antiviral Res. 1997;36:99 -105.
    • 37. Cao Z, Wu HK, Bruce A, Wollenberg K, Panjwani N. Detection of differentially expressed genes in healing mouse corneas, using cDNA microarrays. Invest Ophthalmol Vis Sci. 2002;43:2897- 2904.
    • 38. Carrington L, McLeod D, Boulton M. IL-10 and antibodies to TGFbeta(2) and PDGF inhibit RPE-mediated retinal contraction. Invest Ophthalmol Vis Sci. 2000;41:1210 -1216.
    • 39. Reitamo S, Remitz A, Tamai K, Uitto J. Interleukin-10 modulates type I collagen and matrix metalloproteinase gene expression in cultured human skin fibroblasts. J Clin Invest. 1994;94:2489 - 2492.
    • 40. Arai T, Abe K, Matsuoka H, et al. Introduction of the interleukin-10 gene into mice inhibited bleomycin-induced lung injury in vivo. Am J Physiol Lung Cell Mol Physiol. 2000;278:L914 -L922.
    • 41. Vasse M, Paysant I, Soria J, Mirshahi SS, Vannier JP, Soria C. Down-regulation of fibrinogen biosynthesis by IL-4, IL-10 and IL13. Br J Haematol. 1996;93:955-961.
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