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Corneal Healing

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Part of the book series: Essentials in Ophthalmology ((ESSENTIALS))

Abstract

Corneal wound healing is a complex procedure that involves apoptosis, migration, proliferation, and differentiation of cells. Several growth factors and cytokines are necessary to perform this process. Due to the avascular nature of the cornea, these growth factors proceed from sources such as tears, inflammatory cells, epithelium, or stroma. Depending on the extent and type of injury, the healing response can produce corneal scarring, with loss of corneal transparency leading to visual impairment.

In this chapter, we are going to describe the different cytokines and growth factors involved in the healing procedure, as the different phases during the recovery of each corneal layer.

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References

  1. Dawson D, Ubels JL, Edelhauser HF. Cornea and sclera. In: Levin LA, Alm A, Nilsson SFE, Ver Hoeve J, Wu S, editors. Adler’s physiology of the eye. Edinburgh: Saunders; 2011. p. 71–130.

    Chapter  Google Scholar 

  2. Agrawal VB, Tsai RJF. Corneal epithelial wound healing. Indian J Ophthalmol. 2003;51:5–1.

    PubMed  Google Scholar 

  3. Nishida T, Saika S, Morishige N. Cornea and sclera: anatomy and physiology. In: Krachmer J, Mannis M, Holland E, editors. Cornea. St. Louis: Mosby; 2011. p. 1–22.

    Google Scholar 

  4. Sotozono C, He J, Matsimoto Y, Kita M, Imanishi J, Kinoshita S. Cytokine expression in the alkali-burned cornea. Curr Eye Res. 1997;16:670–6.

    Article  CAS  Google Scholar 

  5. Ashby BD, Garrett Q, Willcox MDP. Corneal injuries and wound healing – review of processes and therapies. Austin J Clin Ophthalmol. 2014;1(4):1017.

    Google Scholar 

  6. Liu C-Y, Kao WW-Y. Corneal epithelial wound healing. Prog Mol Biol Transl Sci. 2015;5:1–11.

    Google Scholar 

  7. Ljubimov AV, Saghizadeh M. Progress in corneal wound healing. Prog Retin Eye Res. 2015;49:17. https://doi.org/10.1016/j.preteyeres.2015.07.002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Sugioka K, Mishima H, Kodama A, Itahashi M, Fukuda M, Shimomura Y. Regulatory mechanism of collagen degradation by keratocytes and corneal inflammation: the role of Urokinase-type plasminogen activator. Cornea. 2016;35(Suppl):S59–64.

    Article  Google Scholar 

  9. Klenkler B, Sheardown H, Jones L. Growth factors in the tear film: role in tissue maintenance, wound healing, and ocular pathology. Ocul Surf. 2007;5(3):228–39.

    Article  Google Scholar 

  10. Imanishi J, Kamiyama K, Iguchi I, Kita M, Sotozono C, Kinoshita S. Growth factors: importance in wound healing and maintenance of transparency of the cornea. Prog Retin Eye Res. 2000;19(1):113–29.

    Article  CAS  Google Scholar 

  11. Miyagi H, Thomasy SM, Russell P, Murphy CJ. The role of hepatocyte growth factor in corneal wound healing. Exp Eye Res. 2018;166:49–55.

    Article  CAS  Google Scholar 

  12. Omoto M, Suri K, Amouzegar A, Li M, Katikireddy KR, Mittal SK, et al. Hepatocyte growth factor suppresses inflammation and promotes epithelium repair in corneal injury. Mol Ther. 2017;25(8):1–8.

    Article  Google Scholar 

  13. Lambiase A, Sacchetti M, Bonini S. Nerve growth factor therapy for corneal disease. Curr Opin Ophthalmol. 2012;23:296–302.

    Article  Google Scholar 

  14. Saghizadeh M, Kramerov AA, Svendsen CN, Ljubimov AV. Concise review: stem cells for corneal wound healing. Stem Cells. 2017;35:2105–14.

    Article  Google Scholar 

  15. Dua HS, Gomes JAP, Singh A. Corneal epithelial wound healing. Br J Ophthalmol. 1994;78:401–8.

    Article  CAS  Google Scholar 

  16. Torricelli A, Santhanam A, Wu J, Singh V, Wilson S. The corneal fibrosis response to epithelial-stromal injury. Exp Eye Res. 2016;142:110–8.

    Article  CAS  Google Scholar 

  17. Bukowiecki A, Hos D, Cursiefen C, Eming SA. Wound-healing studies in cornea and skin: parallels, differences and opportunities. Int J Mol Sci. 2017;18:1–24.

    Article  Google Scholar 

  18. Wilson SE. Corneal myofibroblast biology and pathobiology: generation, persistence and transparency. Exp Eye Res. 2012;99(1):78–88. https://doi.org/10.1016/j.exer.2012.03.018.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Marino GK, Santhiago MR, Torricelli AAM, Santhanam A, Wilson SE. Corneal molecular and cellular biology for the refractive surgeon: the critical role of the epithelial basement membrane. J Refract Surg. 2016;32(2):118–25.

    Article  Google Scholar 

  20. Bonini S, Lambiase A, Rama P, Caprioglio G, Aloe L. Topical treatment with nerve growth factor for neurotrophic keratitis. Ophthalmology. 2000;107:1347–52.

    Article  CAS  Google Scholar 

  21. Cellini M, Bendo E, Bravetti GO, Campos EC. The use of nerve growth factor in surgical wound healing of the cornea. Ophthalmic Res. 2006;38:177–81.

    Article  CAS  Google Scholar 

  22. Lambiase A, Bonini S, Aloe L, et al. Anti-inflammatory and healing properties of nerve growth factor in immune corneal ulcers with stromal melting. Arch Ophthalmol. 2000;118:1446–9.

    Article  CAS  Google Scholar 

  23. Nishida T, Chikama T, Morishige N, Yanai R, Yamada N, Saito J. Persistent epithelial defects due to neurotrophic keratopathy treated with a substance P- derived peptide and insulin-like growth factor 1. Jpn J Ophthalmol. 2007;51:442–7.

    Article  CAS  Google Scholar 

  24. Yamada N, Matsuda R, Morishige N, Yanai R, Chikama T-i, Nishida T, Ishimitsu T, Kamiya A. Open clinical study of eye-drops containing tetrapeptides derived from substance P and insulin-like growth factor-1 for treatment or persistent corneal epithelial defects associated with neurotrophic keratopathy. Br J Ophthalmol. 2008;92:896–900.

    Article  CAS  Google Scholar 

  25. Holland S, Morck D, Schultz C. Treatment of corneal defects with delayed re-epithelization with a medical device/drug delivery system for epidermal growth factor. Clin Exp Ophthalmol. 2012;40:1–6. https://doi.org/10.1111/j.1442-9071.2012.02795.x.

    Article  Google Scholar 

  26. Alió JL, Arnalich-Montiel F, Rodriguez AE. The role of “eye platelet rich plasma” (E-Prp) for wound healing in ophthalmology. Curr Pharm Biotechnol. 2012;13:1257–65.

    Article  Google Scholar 

  27. Alio JL, Abad M, Artola A, Rodriguez-Prats JL, Pastor S, Ruiz-Colecha J. Use of autologous platelet-rich plasma in the treatment of dormant corneal ulcers. Ophthalmology. 2007;114(7):1286–93.

    Article  Google Scholar 

  28. Waring GO, Bourne WM, Edelhauser HF, Kenyon KR. The corneal endothelium. Normal and pathologic structure and function. Ophthalmology. 1982;89(6):531–90.

    Article  Google Scholar 

  29. Edelhauser HF. The resiliency of the corneal endothelium to refractive and intraocular surgery. Cornea. 2000;19(3):263–73.

    Article  CAS  Google Scholar 

  30. Joyce NC. Proliferative capacity of the corneal endothelium. Prog Retin Eye Res. 2003;22(3):359–89.

    Article  CAS  Google Scholar 

  31. Watsky MA, McDermott ML, Edelhauser HF. In vitro corneal endothelial permeability in rabbit and human: the effects of age, cataract surgery and diabetes. Exp Eye Res. 1989;49(5):751–67.

    Article  CAS  Google Scholar 

  32. Senoo T, Joyce NC. Cell cycle kinetics in corneal endothelium from old and young donors. Invest Ophthalmol Vis Sci. 2000;41(3):660–7.

    CAS  PubMed  Google Scholar 

  33. Yoshida K, Kase S, Nakayama K, Nagahama H, Harada T, Ikeda H, et al. Involvement of p27KIP1 in the proliferation of the developing corneal endothelium. Invest Ophthalmol Vis Sci. 2004;45(7):2163–7.

    Article  Google Scholar 

  34. 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(5):2116–22.

    Article  Google Scholar 

  35. Van den Bogerd B, Dhubhghaill SN, Koppen C, Tassignon M-J, Zakaria N. A review of the evidence for in vivo corneal endothelial regeneration. Surv Ophthalmol. 2018;63:149–65.

    Article  Google Scholar 

  36. Dirisamer M, Ham L, Dapena I, van Dijk K, Melles GRJ. Descemet membrane endothelial transfer: “free-floating” donor descemet implantation as a potential alternative to “keratoplasty”. Cornea. 2012;31(2):194–7.

    Article  Google Scholar 

  37. Okumura N, Ueno M, Koizumi N, Sakamoto Y, Hirata K, Hamuro J, et al. Enhancement on primate corneal endothelial cell survival in vitro by a ROCK inhibitor. Invest Ophthalmol Vis Sci. 2009;50(8):3680–7.

    Article  Google Scholar 

  38. Okumura N, Okazaki Y, Inoue R, Kakutani K, Nakano S, Kinoshita S, et al. Effect of the Rho-associated kinase inhibitor eye drop (Ripasudil) on corneal endothelial wound healing. Invest Ophthalmol Vis Sci. 2016;57(3):1284–92.

    Article  CAS  Google Scholar 

  39. Okumura N, Sakamoto Y, Fujii K, Kitano J, Nakano S, Tsujimoto Y, et al. Rho kinase inhibitor enables cell-based therapy for corneal endothelial dysfunction. Sci Rep. 2016;6(1):26113.

    Article  CAS  Google Scholar 

  40. Okumura N, Inoue R, Okazaki Y, Nakano S, Nakagawa H, Kinoshita S, et al. Effect of the Rho kinase inhibitor Y-27632 on corneal endothelial wound healing. Investig Opthalmology Vis Sci. 2015;56(10):6067.

    Article  CAS  Google Scholar 

  41. Moloney G, Petsoglou C, Ball M, Kerdraon Y, Höllhumer R, Spiteri N, et al. Descemetorhexis without grafting for fuchs endothelial dystrophy-supplementation with topical Ripasudil. Cornea. 2017;36(6):642–8.

    Article  Google Scholar 

  42. Koizumi N, Okumura N, Ueno M, Nakagawa H, Hamuro J, Kinoshita S. Rho-associated kinase inhibitor eye drop treatment as a possible medical treatment for Fuchs corneal dystrophy. Cornea. 2013;32(8):1167–70.

    Article  Google Scholar 

  43. Lam FC, Baydoun L, Dirisamer M, Lie J, Dapena I, Melles GRJ. Hemi-Descemet membrane endothelial keratoplasty transplantation: a potential method for increasing the pool of endothelial graft tissue. JAMA Ophthalmol. 2014;132(12):1469–73.

    Article  Google Scholar 

  44. Lam FC, Bruinsma M, Melles GRJ. Descemet membrane endothelial transfer. Curr Opin Ophthalmol. 2014;25(4):353–7.

    Article  Google Scholar 

  45. 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.

    Article  CAS  Google Scholar 

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Vargas, V., Arnalich-Montiel, F., Alió del Barrio, J.L. (2019). Corneal Healing. In: Alió, J., Alió del Barrio, J., Arnalich-Montiel, F. (eds) Corneal Regeneration . Essentials in Ophthalmology. Springer, Cham. https://doi.org/10.1007/978-3-030-01304-2_2

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  • DOI: https://doi.org/10.1007/978-3-030-01304-2_2

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-01303-5

  • Online ISBN: 978-3-030-01304-2

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