Advertisement

Anatomy and Physiology: Considerations in Relation to Transplantation

  • Ursula Schlötzer-SchrehardtEmail author
  • Friedrich E. Kruse
Chapter

Abstract

Over the past decade, corneal transplantation has evolved rapidly from full-thickness penetrating keratoplasty toward partial-thickness or lamellar keratoplasty. Lamellar corneal surgery is in continuous evolution, which requires an understanding of the structural, biomechanical, and histological characteristics of corneal layers involved. In this chapter, we describe the anatomy and physiology of the human cornea in order to provide the structural basis for understanding the newly developed techniques. The chapter provides detailed information on morphological, histological, ultrastructural, and physiological characteristics of the five anatomical corneal layers, i.e., epithelium, Bowman’s layer, corneal stroma consisting of regularly arranged collagen fibrils interspersed with keratocytes, Descemet’s membrane, and endothelial cells, in relation to corneal transplantation. In particular, it outlines regional and age-related differences in structure, biomechanical properties, mechanisms of wound healing and restoration of corneal transparency, causes of stromal haze, cleavage planes and interface characteristics in lamellar transplantation techniques, and reasons for graft failure. Patterns of corneal innervation and the molecular mechanisms of antiangiogenic and immune privileges, which determine the success of allogeneic corneal transplantation, are described in addition.

Keywords

Epithelium Bowman’s layer Stroma Descemet’s membrane Endothelium Anatomy Histology Electron microscopy Corneal innervation Immune privilege 

References

  1. 1.
    Ahmad S. Concise review: limbal stem cell deficiency, dysfunction, and distress. Stem Cells Transl Med. 2012;1:110–5.PubMedCentralCrossRefPubMedGoogle Scholar
  2. 2.
    Albuquerque RJ, Hayashi T, Cho WG, Kleinman ME, Dridi S, Takeda A, Baffi JZ, Yamada K, Kaneko H, Green MG, Chappell J, Wilting J, Weich HA, Yamagami S, Amano S, Mizuki N, Alexander JS, Peterson ML, Brekken RA, Hirashima M, Capoor S, Usui T, Ambati BK, Ambati J. Alternatively spliced vascular endothelial growth factor receptor-2 is an essential endogenous inhibitor of lymphatic vessel growth. Nat Med. 2009;15:1023–30.PubMedCentralCrossRefPubMedGoogle Scholar
  3. 3.
    Anwar M, Teichmann KD. Deep lamellar keratoplasty: surgical techniques for anterior lamellar keratoplasty with and without baring of Descemet’s membrane. Cornea. 2002;21:374–83.CrossRefPubMedGoogle Scholar
  4. 4.
    Arenas E, Esquenazi S, Anwar M, Terry M. Lamellar corneal transplantation. Surv Ophthalmol. 2012;57:510–29.CrossRefPubMedGoogle Scholar
  5. 5.
    Azar DT. Corneal angiogenic privilege: angiogenic and antiangiogenic factors in corneal avascularity, vasculogenesis, and wound healing (an American Ophthalmological Society thesis). Trans Am Ophthalmol Soc. 2006;104:264–302.PubMedCentralPubMedGoogle Scholar
  6. 6.
    Bahn CF, Glassman RM, MacCallum DK, Lillie JH, Meyer RF, Robinson BJ, Rich NM. Postnatal development of corneal endothelium. Invest Ophthalmol Vis Sci. 1986;27:44–51.PubMedGoogle Scholar
  7. 7.
    Beebe DC, Masters BR. Cell lineage and the differentiation of corneal epithelial cells. Invest Ophthalmol Vis Sci. 1996;37:1815–25.PubMedGoogle Scholar
  8. 8.
    Blitzer AL, Panagis L, Gusella GL, Danias J, Mlodzik M, Iomini C. Primary cilia dynamics instruct tissue patterning and repair of corneal endothelium. Proc Natl Acad Sci U S A. 2011;108:2819–24.PubMedCentralCrossRefPubMedGoogle Scholar
  9. 9.
    Bonanno JA. Molecular mechanisms underlying the corneal endothelial pump. Exp Eye Res. 2012;95:2–7.PubMedCentralCrossRefPubMedGoogle Scholar
  10. 10.
    Bonini S, Rama P, Olzi D, Lambiase A. Neurotrophic keratitis. Eye (Lond). 2003;17:989–95.CrossRefGoogle Scholar
  11. 11.
    Boote C, Dooley EP, Gardner SJ, Kamma-Lorger CS, Hayes S, Nielsen K, Hjortdal J, Sorensen T, Terrill NJ, Meek KM. Quantification of collagen ultrastructure after penetrating keratoplasty – implications for corneal biomechanics. PLoS One. 2013;8, e68166.PubMedCentralCrossRefPubMedGoogle Scholar
  12. 12.
    Bucher F, Hos D, Matthaei M, Steven P, Cursiefen C, Heindl LM. Corneal nerve alterations after descemet membrane endothelial keratoplasty: an in vivo confocal microscopy study. Cornea. 2014;33:1134–9.CrossRefPubMedGoogle Scholar
  13. 13.
    Chen ES, Shamie N, Terry MA, Phillips PM, Wilson DJ. Retention of host embryonic descemet membrane in endothelial keratoplasty. Cornea. 2009;28:351–3.CrossRefPubMedGoogle Scholar
  14. 14.
    Cirkovic A, Schlötzer-Schrehardt U, Weller JM, Kruse FE, Tourtas T. Clinical and ultrastructural characteristics of graft failure in DMEK: 1-year results after repeat DMEK. Cornea. 2015;34:11–7.CrossRefPubMedGoogle Scholar
  15. 15.
    Cotsarelis G, Cheng SZ, Dong G, Sun TT, Lavker RM. Existence of slow-cycling limbal epithelial basal cells that can be preferentially stimulated to proliferate: implications on epithelial stem cells. Cell. 1989;57:201–9.CrossRefPubMedGoogle Scholar
  16. 16.
    Cruzat A, Witkin D, Baniasadi N, Zheng L, Ciolino JB, Jurkunas UV, Chodosh J, Pavan-Langston D, Dana R, Hamrah P. Inflammation and the nervous system: the connection in the cornea in patients with infectious keratitis. Invest Ophthalmol Vis Sci. 2011;52:5136–43.PubMedCentralCrossRefPubMedGoogle Scholar
  17. 17.
    Cursiefen C, Kruse FE, Naumann GOH. Special anatomy and pathology in intraocular microsurgery: cornea and limbus. In: Naumann GOH, Holbach L, Kruse FE, editors. Applied pathology for ophthalmic microsurgeons. Berlin/Heidelberg: Springer; 2008. p. 97–130.CrossRefGoogle Scholar
  18. 18.
    DelMonte DW, Kim T. Anatomy and physiology of the cornea. J Cataract Refract Surg. 2011;37:588–98.CrossRefPubMedGoogle Scholar
  19. 19.
    Dua HS, Faraj LA, Said DG, Gray T, Lowe J. Human corneal anatomy redefined: a novel pre-Descemet’s layer (Dua’s layer). Ophthalmology. 2013;120:1778–85.CrossRefPubMedGoogle Scholar
  20. 20.
    Dua HS, Faraj LA, Branch MJ, Yeung AM, Elalfy MS, Said DG, Gray T, Lowe J. The collagen matrix of the human trabecular meshwork is an extension of the novel pre-Descemet’s layer (Dua’s layer). Br J Ophthalmol. 2014;98:691–7.CrossRefPubMedGoogle Scholar
  21. 21.
    Feng MT, Price MO, Miller JM, Price Jr FW. Air reinjection and endothelial cell density in Descemet membrane endothelial keratoplasty: five-year follow-up. J Cataract Refract Surg. 2014;40:1116–21.CrossRefPubMedGoogle Scholar
  22. 22.
    Garcia-Hirschfeld J, Lopez-Briones LG, Belmonte C. Neurotrophic influences on corneal epithelial cells. Exp Eye Res. 1994;59:597–605.CrossRefPubMedGoogle Scholar
  23. 23.
    Germundsson J, Karanis G, Fagerholm P, Lagali N. Age-related thinning of Bowman’s layer in the human cornea in vivo. Invest Ophthalmol Vis Sci. 2013;54:6143–9.CrossRefPubMedGoogle Scholar
  24. 24.
    Geroski DH, Matsuda M, Yee RW, Edelhauser HF. Pump function of the human corneal endothelium. Effects of age and cornea guttata. Ophthalmology. 1985;92:759–63.CrossRefPubMedGoogle Scholar
  25. 25.
    Gipson IK. Adhesive mechanisms of the corneal epithelium. Acta Ophthalmol Suppl. 1992;202:13–7.PubMedGoogle Scholar
  26. 26.
    Gipson IK. Distribution of mucins at the ocular surface. Exp Eye Res. 2004;78:379–88.CrossRefPubMedGoogle Scholar
  27. 27.
    Hassell JR, Birk DE. The molecular basis of corneal transparency. Exp Eye Res. 2010;91:326–35.PubMedCentralCrossRefPubMedGoogle Scholar
  28. 28.
    Heindl LM, Schlötzer-Schrehardt U, Cursiefen C, Bachmann BO, Hofmann-Rummelt C, Kruse FE. Myofibroblast metaplasia after descemet membrane endothelial keratoplasty. Am J Ophthalmol. 2011;151:1019–23.CrossRefPubMedGoogle Scholar
  29. 29.
    Honda N, Mimura T, Usui T, Amano S. Descemet stripping automated endothelial keratoplasty using cultured corneal endothelial cells in a rabbit model. Arch Ophthalmol. 2009;127:1321–6.CrossRefPubMedGoogle Scholar
  30. 30.
    Jacobi C, Zhivov A, Korbmacher J, Falke K, Guthoff R, Schlötzer-Schrehardt U, Cursiefen C, Kruse FE. Evidence of endothelial cell migration after descemet membrane endothelial keratoplasty. Am J Ophthalmol. 2011;152:537–42.CrossRefPubMedGoogle Scholar
  31. 31.
    Jafarinasab MR, Rahmati-Kamel M, Kanavi MR, Feizi S. Dissection plane in deep anterior lamellar keratoplasty using the big-bubble technique. Cornea. 2010;29:388–91.CrossRefPubMedGoogle Scholar
  32. 32.
    Jester JV, Moller-Pedersen T, Huang J, Sax CM, Kays WT, Cavangh HD, Petroll WM, Piatigorsky J. The cellular basis of corneal transparency: evidence for ‘corneal crystallins’. J Cell Sci. 1999;112:613–22.PubMedGoogle Scholar
  33. 33.
    Johnson DH, Bourne WM, Campbell RJ. The ultrastructure of Descemet’s membrane. I. Changes with age in normal corneas. Arch Ophthalmol. 1982;100:1942–7.CrossRefPubMedGoogle Scholar
  34. 34.
    Joyce NC. Proliferative capacity of corneal endothelial cells. Exp Eye Res. 2012;95:16–23.PubMedCentralCrossRefPubMedGoogle Scholar
  35. 35.
    Kenyon KR, Tseng SC. Limbal autograft transplantation for ocular surface disorders. Ophthalmology. 1989;96:709–22.CrossRefPubMedGoogle Scholar
  36. 36.
    Kim SY, Muftuoglu O, Hogan RN, Bowman RW, Cavanagh HD, McCulley JP, Mootha VV. Histopathology and spectral domain OCT findings of pneumatic-assisted dissection in DALK. Cornea. 2012;31:1288–93.CrossRefPubMedGoogle Scholar
  37. 37.
    Knickelbein JE, Buela KA, Hendricks RL. Antigen-presenting cells are stratified within normal human corneas and are rapidly mobilized during ex vivo viral infection. Invest Ophthalmol Vis Sci. 2014;55:1118–23.PubMedCentralCrossRefPubMedGoogle Scholar
  38. 38.
    Komai Y, Ushiki T. The three-dimensional organization of collagen fibrils in the human cornea and sclera. Invest Ophthalmol Vis Sci. 1991;32:2244–58.PubMedGoogle Scholar
  39. 39.
    Kremer I, Rapuano CJ, Cohen EJ, Laibson PR, Eagle Jr RC. Retrocorneal fibrous membranes in failed corneal grafts. Am J Ophthalmol. 1993;115:478–83.CrossRefPubMedGoogle Scholar
  40. 40.
    Kruse FE, Laaser K, Cursiefen C, et al. A stepwise approach to donor preparation and insertion increases safety and outcome of Descemet membrane endothelial keratoplasty. Cornea. 2011;30:580–7.PubMedGoogle Scholar
  41. 41.
    Kruse FE, Schlötzer-Schrehardt U, Tourtas T. Optimizing outcomes with Descemet’s membrane endothelial keratoplasty. Curr Opin Ophthalmol. 2014;25:325–34.CrossRefPubMedGoogle Scholar
  42. 42.
    Laaser K, Bachmann BO, Horn FK, Schlötzer-Schrehardt U, Cursiefen C, Kruse FE. Donor tissue culture conditions and outcome after descemet membrane endothelial keratoplasty. Am J Ophthalmol. 2011;151:1007–18.CrossRefPubMedGoogle Scholar
  43. 43.
    McKee HD, Irion LC, Carley FM, Jhanji V, Brahma AK. Residual corneal stroma in big-bubble deep anterior lamellar keratoplasty: a histological study in eye-bank corneas. Br J Ophthalmol. 2011;95:1463–5.CrossRefPubMedGoogle Scholar
  44. 44.
    Meek KM, Leonard DW. Ultrastructure of the corneal stroma: a comparative study. Biophys J. 1993;64:273–80.PubMedCentralCrossRefPubMedGoogle Scholar
  45. 45.
    Meek KM, Boote C. The organization of collagen in the corneal stroma. Exp Eye Res. 2004;78:503–12.CrossRefPubMedGoogle Scholar
  46. 46.
    Meek KM, Leonard DW, Connon CJ, Dennis S, Khan S. Transparency, swelling and scarring in the corneal stroma. Eye (Lond). 2003;17:927–36.CrossRefGoogle Scholar
  47. 47.
    Melles GR, Ong TS, Ververs B, van der Wees J. Descemet membrane endothelial keratoplasty (DMEK). Cornea. 2006;25:987–90.CrossRefPubMedGoogle Scholar
  48. 48.
    Michelacci YM. Collagens and proteoglycans of the corneal extracellular matrix. Braz J Med Biol Res. 2003;36:1037–46.CrossRefPubMedGoogle Scholar
  49. 49.
    Mondloch MC, Giegengack M, Terry MA, Wilson DJ. Histologic evidence of retained fetal layer of the descemet membrane after presumed total removal for endothelial keratoplasty: a possible cause for graft failure. Cornea. 2007;26:1263–6.CrossRefPubMedGoogle Scholar
  50. 50.
    Müller LJ, Pels L, Vrensen GF. Novel aspects of the ultrastructural organization of human corneal keratocytes. Invest Ophthalmol Vis Sci. 1995;36:2557–67.PubMedGoogle Scholar
  51. 51.
    Müller LJ, Pels E, Vrensen GF. The specific architecture of the anterior stroma accounts for maintenance of corneal curvature. Br J Ophthalmol. 2001;85:437–43.PubMedCentralCrossRefPubMedGoogle Scholar
  52. 52.
    Müller LJ, Marfurt CF, Kruse F, Tervo TM. Corneal nerves: structure, contents and function. Exp Eye Res. 2003;76:521–42.CrossRefPubMedGoogle Scholar
  53. 53.
    Müller LJ, Pels E, Schurmans LR, Vrensen GF. A new three-dimensional model of the organization of proteoglycans and collagen fibrils in the human corneal stroma. Exp Eye Res. 2004;78:493–501.CrossRefPubMedGoogle Scholar
  54. 54.
    Murphy C, Alvarado J, Juster R. Prenatal and postnatal growth of the human Descemet’s membrane. Invest Ophthalmol Vis Sci. 1984;25:1402–15.PubMedGoogle Scholar
  55. 55.
    Niederkorn JY. Corneal transplantation and immune privilege. Int Rev Immunol. 2013;32:57–67.CrossRefPubMedGoogle Scholar
  56. 56.
    Okumura N, Kinoshita S, Koizumi N. Cell-based approach for treatment of corneal endothelial dysfunction. Cornea. 2014;33 Suppl 11:S37–41.CrossRefPubMedGoogle Scholar
  57. 57.
    Patel SV, Erie JC, McLaren JW, Bourne WM. Keratocyte and subbasal nerve density after penetrating keratoplasty. Trans Am Ophthalmol Soc. 2007;105:180–9.PubMedCentralPubMedGoogle Scholar
  58. 58.
    Peh GS, Beuerman RW, Colman A, Tan DT, Mehta JS. Human corneal endothelial cell expansion for corneal endothelium transplantation: an overview. Transplantation. 2011;91:811–9.CrossRefPubMedGoogle Scholar
  59. 59.
    Poole CA, Brookes NH, Clover GM. Confocal imaging of the human keratocyte network using the vital dye 5-chloromethylfluorescein diacetate. Clin Experiment Ophthalmol. 2003;31:147–54.CrossRefPubMedGoogle Scholar
  60. 60.
    Poothullil AM, Gipson IK. Cornea: structural features and wound healing. In: John T, editor. Lamellar corneal surgery. New York: The McGraw-Hill Companies; 2008. p. 3–14.Google Scholar
  61. 61.
    Price Jr FW, Price MO. Descemet’s stripping with endothelial keratoplasty in 50 eyes: a refractive neutral corneal transplant. J Refract Surg. 2005;21:339–45.PubMedGoogle Scholar
  62. 62.
    Proulx S, Bensaoula T, Nada O, Audet C, d’Arc Uwamaliya J, Devaux A, Allaire G, Germain L, Brunette I. Transplantation of a tissue-engineered corneal endothelium reconstructed on a devitalized carrier in the feline model. Invest Ophthalmol Vis Sci. 2009;50:2686–94.CrossRefPubMedGoogle Scholar
  63. 63.
    Rajan MS. Surgical strategies to improve visual outcomes in corneal transplantation. Eye. 2014;28:196–201.PubMedCentralCrossRefPubMedGoogle Scholar
  64. 64.
    Schlötzer-Schrehardt U, Bachmann BO, Laaser K, Cursiefen C, Kruse FE. Characterization of the cleavage plane in Descemet’s membrane endothelial keratoplasty. Ophthalmology. 2011;118:1950–7.CrossRefPubMedGoogle Scholar
  65. 65.
    Schlötzer-Schrehardt U, Bachmann BO, Tourtas T, Cursiefen C, Zenkel M, Rössler K, Kruse FE. Reproducibility of graft preparations in Descemet’s membrane endothelial keratoplasty. Ophthalmology. 2013;120:1769–77.CrossRefPubMedGoogle Scholar
  66. 66.
    Schlötzer-Schrehardt U, Bachmann BO, Tourtas T, Torricelli AA, Singh A, Gonzalez S, Mei H, Deng SX, Wilson SE, Kruse FE. Ultrastructure of the posterior corneal stroma. Ophthalmology. 2015;122:693–9.CrossRefPubMedGoogle Scholar
  67. 67.
    Shortt AJ, Secker GA, Notara MD, Limb GA, Khaw PT, Tuft SJ, Daniels JT. Transplantation of ex vivo cultured limbal epithelial stem cells: a review of techniques and clinical results. Surv Ophthalmol. 2007;52:483–502.CrossRefPubMedGoogle Scholar
  68. 68.
    Stachs O, Zhivov A, Kraak R, Hovakimyan M, Wree A, Guthoff R. Structural-functional correlations of corneal innervation after LASIK and penetrating keratoplasty. J Refract Surg. 2010;26:159–67.PubMedGoogle Scholar
  69. 69.
    Tan DT, Dart JK, Holland EJ, Kinoshita S. Corneal transplantation. Lancet. 2012;379:1749–61.CrossRefPubMedGoogle Scholar
  70. 70.
    Tiffany JM. The normal tear film. Dev Ophthalmol. 2008;41:1–20.CrossRefPubMedGoogle Scholar
  71. 71.
    Torricelli AA, Wilson SE. Cellular and extracellular matrix modulation of corneal stromal opacity. Exp Eye Res. 2014;129:151–60.CrossRefPubMedGoogle Scholar
  72. 72.
    Tourtas T, Laaser K, Bachmann BO, Cursiefen C, Kruse FE. Descemet membrane endothelial keratoplasty versus descemet stripping automated endothelial keratoplasty. Am J Ophthalmol. 2012;153:1082–90.CrossRefPubMedGoogle Scholar
  73. 73.
    Tourtas T, Schlomberg J, Wessel JM, Bachmann BO, Schlötzer-Schrehardt U, Kruse FE. Graft adhesion in Descemet membrane endothelial keratoplasty dependent on size of removal of host’s Descemet membrane. JAMA Ophthalmol. 2014;132:155–61.CrossRefPubMedGoogle Scholar
  74. 74.
    Tsubota K, Mashima Y, Murata H, Yamada M, Sato N. Corneal epithelium following penetrating keratoplasty. Br J Ophthalmol. 1995;79:257–60.PubMedCentralCrossRefPubMedGoogle Scholar
  75. 75.
    Waring 3rd GO. Posterior collagenous layer of the cornea. Ultrastructural classification of abnormal collagenous tissue posterior to Descemet’s membrane in 30 cases. Arch Ophthalmol. 1982;100:122–34.CrossRefPubMedGoogle Scholar
  76. 76.
    Weller JM, Tourtas T, Kruse FE, Schlötzer-Schrehardt U, Fuchsluger T, Bachmann BO. Descemet membrane endothelial keratoplasty as treatment for graft failure after Descemet stripping automated endothelial keratoplasty. Am J Ophthalmol. 2015;159:1050–7.Google Scholar
  77. 77.
    Wilson SE, Hong JW. Bowman’s layer structure and function: critical or dispensable to corneal function? A hypothesis. Cornea. 2000;19:417–20.CrossRefPubMedGoogle Scholar
  78. 78.
    Wilson SE, Chaurasia SS, Medeiros FW. Apoptosis in the initiation, modulation and termination of the corneal wound healing response. Exp Eye Res. 2007;85:305–11.PubMedCentralCrossRefPubMedGoogle Scholar
  79. 79.
    Zhang Q, Randleman JB, Stulting RD, Lee WB, Stone DU, Kozarsky AM, Grossniklaus HE. Clinicopathologic findings in failed Descemet stripping automated endothelial keratoplasty. Arch Ophthalmol. 2010;128:973–80.PubMedCentralCrossRefPubMedGoogle Scholar
  80. 80.
    Zieske JD. Extracellular matrix and wound healing. Curr Opin Ophthalmol. 2001;12:237–41.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Ursula Schlötzer-Schrehardt
    • 1
    Email author
  • Friedrich E. Kruse
    • 1
  1. 1.Department of OphthalmologyUniversity of Erlangen-NürnbergErlangenGermany

Personalised recommendations