Abstract
The cornea is a uniquely translucent, avascular tissue located on the anterior segment of the eye. It is surrounded and maintained by the adjacent corneoscleral limbus and the connective tissue of the conjunctiva with its adnexa. It plays a vital role in visual function by providing (1) the major refractive component of the visual system, (2) a translucent tissue that allows light passage to the lens and retina, and (3) a barrier that protects the eye from fluid loss and the external environment. These crucial functions result from the structure of the cornea, which is composed of three anatomical layers: epithelium, stroma, and endothelium. The limbus is the reservoir for the adult stem cell population that replenishes the cornea and is the site of termination of the vasculature and entry of the nerves that provide an extraordinarily rich innervation environment.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Gipson IK, Joyce NC. Anatomy and cell biology of the cornea, superficial limbus and conjunctiva. In: Albert D, Miller J, Azar D, Blodi B, editors. Albert & Jakobiec’s principles and practice of ophthalmology. Philadelphia/Edinburgh: Saunders/Elsevier; 2008. p. 423–40.
Gipson IK, Joyce NJ, Zieske JD. The anatomy and cell biology of the human cornea, limbus, conjunctiva, and adnexa. In: Foster CS, Azar DT, Dohlman CH, editors. Smolin and Thoft’s the cornea : scientific foundations and clinical practice. Philadelphia: Lippincott Williams & Wilkins; 2005. p. 1–35.
Lwigale PY. Corneal development: different cells from a common progenitor. Prog Mol Biol Transl Sci. 2015;134:43–59.
Collomb E, Yang Y, Foriel S, Cadau S, Pearton DJ, Dhouailly D. The corneal epithelium and lens develop independently from a common pool of precursors. Dev Dyn. 2013;242:401–13.
Creuzet S, Vincent C, Couly G. Neural crest derivatives in ocular and periocular structures. Int J Dev Biol. 2005;49:161–71.
Lwigale PY, Cressy PA, Bronner-Fraser M. Corneal keratocytes retain neural crest progenitor cell properties. Dev Biol. 2005;288:284–93.
Greene CA, Green CR, Dickinson ME, Johnson V, Sherwin T. Keratocytes are induced to produce collagen type II: a new strategy for in vivo corneal matrix regeneration. Exp Cell Res. 2016;347:241–9.
Rufer F, Schroder A, Erb C. White-to-white corneal diameter: normal values in healthy humans obtained with the Orbscan II topography system. Cornea. 2005;24:259–61.
Khng C, Osher RH. Evaluation of the relationship between corneal diameter and lens diameter. J Cataract Refract Surg. 2008;34:475–9.
Doughty MJ, Zaman ML. Human corneal thickness and its impact on intraocular pressure measures: a review and meta-analysis approach. Surv Ophthalmol. 2000;44:367–408.
Randleman JB, Lynn MJ, Perez-Straziota CE, Weissman HM, Kim SW. Comparison of central and peripheral corneal thickness measurements with scanning-slit, Scheimpflug and Fourier-domain ocular coherence tomography. Br J Ophthalmol. 2015;99:1176–81.
Doughty MJ, Jonuscheit S. An assessment of regional differences in corneal thickness in normal human eyes, using the Orbscan II or ultrasound pachymetry. Optometry. 2007;78:181–90.
Argueso P, Tisdale A, Mandel U, Letko E, Foster CS, Gipson IK. The cell-layer- and cell-type-specific distribution of GalNAc-transferases in the ocular surface epithelia is altered during keratinization. Invest Ophthalmol Vis Sci. 2003;44:86–92.
Gipson IK. Distribution of mucins at the ocular surface. Exp Eye Res. 2004;78:379–88.
Nichols B, Dawson CR, Togni B. Surface features of the conjunctiva and cornea. Invest Ophthalmol Vis Sci. 1983;24:570–6.
Gipson IK, Argueso P. Role of mucins in the function of the corneal and conjunctival epithelia. Int Rev Cytol. 2003;231:1–49.
Gipson IK, Spurr-Michaud S, Tisdale A, Menon BB. Comparison of the transmembrane mucins MUC1 and MUC16 in epithelial barrier function. PLoS One. 2014;9:e100393.
Argueso P, Spurr-Michaud S, Russo CL, Tisdale A, Gipson IK. MUC16 mucin is expressed by the human ocular surface epithelia and carries the H185 carbohydrate epitope. Invest Ophthalmol Vis Sci. 2003;44:2487–95.
Shafiq MA, Gemeinhart RA, Yue BY, Djalilian AR. Decellularized human cornea for reconstructing the corneal epithelium and anterior stroma. Tissue Eng Part C Methods. 2012;18:340–8.
Tuori A, Uusitalo H, Burgeson RE, Terttunen J, Virtanen I. The immunohistochemical composition of the human corneal basement membrane. Cornea. 1996;15:286–94.
Resch MD, Schlotzer-Schrehardt U, Hofmann-Rummelt C, Kruse FE, Seitz B. Alterations of epithelial adhesion molecules and basement membrane components in lattice corneal dystrophy (LCD). Graefes Arch Clin Exp Ophthalmol. 2009;247:1081–8.
Castro-Munozledo F. Review: corneal epithelial stem cells, their niche and wound healing. Mol Vis. 2013;19:1600–13.
Gipson IK. Adhesive mechanisms of the corneal epithelium. Acta Ophthalmol Suppl. 1992;202:13–7.
Gonzalez-Andrades M, Garzon I, Gascon MI, et al. Sequential development of intercellular junctions in bioengineered human corneas. J Tissue Eng Regen Med. 2009;3:442–9.
Colabelli Gisoldi RA, Pocobelli A, Villani CM, Amato D, Pellegrini G. Evaluation of molecular markers in corneal regeneration by means of autologous cultures of limbal cells and keratoplasty. Cornea. 2010;29:715–22.
Shurman DL, Glazewski L, Gumpert A, Zieske JD, Richard G. In vivo and in vitro expression of connexins in the human corneal epithelium. Invest Ophthalmol Vis Sci. 2005;46:1957–65.
Ferrari G, Hajrasouliha AR, Sadrai Z, Ueno H, Chauhan SK, Dana R. Nerves and neovessels inhibit each other in the cornea. Invest Ophthalmol Vis Sci. 2013;54:813–20.
Bonini S, Rama P, Olzi D, Lambiase A. Neurotrophic keratitis. Eye (Lond). 2003;17:989–95.
Muller LJ, Marfurt CF, Kruse F, Tervo TM. Corneal nerves: structure, contents and function. Exp Eye Res. 2003;76:521–42.
Shaheen BS, Bakir M, Jain S. Corneal nerves in health and disease. Surv Ophthalmol. 2014;59:263–85.
Sacchetti M, Lambiase A. Neurotrophic factors and corneal nerve regeneration. Neural Regen Res. 2017;12:1220–4.
Marfurt CF, Cox J, Deek S, Dvorscak L. Anatomy of the human corneal innervation. Exp Eye Res. 2010;90:478–92.
West JD, Dora NJ, Collinson JM. Evaluating alternative stem cell hypotheses for adult corneal epithelial maintenance. World J Stem Cells. 2015;7:281–99.
Lavker RM, Dong G, Cheng SZ, Kudoh K, Cotsarelis G, Sun TT. Relative proliferative rates of limbal and corneal epithelia. Implications of corneal epithelial migration, circadian rhythm, and suprabasally located DNA-synthesizing keratinocytes. Invest Ophthalmol Vis Sci. 1991;32:1864–75.
Yanoff M, Fine BS. Ocular pathology. 5th ed. Philadelphia: Mosby; 2002. xxi, 701 p.
Schlotzer-Schrehardt U, Kruse FE. Identification and characterization of limbal stem cells. Exp Eye Res. 2005;81:247–64.
Menzel-Severing J, Kruse FE, Schlotzer-Schrehardt U. Stem cell-based therapy for corneal epithelial reconstruction: present and future. Can J Ophthalmol. 2013;48:13–21.
Takacs L, Toth E, Berta A, Vereb G. Stem cells of the adult cornea: from cytometric markers to therapeutic applications. Cytometry A. 2009;75:54–66.
Schlotzer-Schrehardt U, Dietrich T, Saito K, et al. Characterization of extracellular matrix components in the limbal epithelial stem cell compartment. Exp Eye Res. 2007;85:845–60.
Notara M, Alatza A, Gilfillan J, et al. In sickness and in health: corneal epithelial stem cell biology, pathology and therapy. Exp Eye Res. 2010;90:188–95.
Ksander BR, Kolovou PE, Wilson BJ, et al. ABCB5 is a limbal stem cell gene required for corneal development and repair. Nature. 2014;511:353–7.
Ramos T, Scott D, Ahmad S. An update on ocular surface epithelial stem cells: cornea and conjunctiva. Stem Cells Int. 2015;2015:601731.
Foster JW, Jones RR, Bippes CA, Gouveia RM, Connon CJ. Differential nuclear expression of Yap in basal epithelial cells across the cornea and substrates of differing stiffness. Exp Eye Res. 2014;127:37–41.
Jones RR, Hamley IW, Connon CJ. Ex vivo expansion of limbal stem cells is affected by substrate properties. Stem Cell Res. 2012;8:403–9.
Li W, Hayashida Y, Chen YT, Tseng SC. Niche regulation of corneal epithelial stem cells at the limbus. Cell Res. 2007;17:26–36.
Hogan MJ, Alvarado JA, Weddell JE. Histology of the human eye. 1st ed. Philadelphia: W.C. Saunders Company; 1971.
Dziasko MA, Tuft SJ, Daniels JT. Limbal melanocytes support limbal epithelial stem cells in 2D and 3D microenvironments. Exp Eye Res. 2015;138:70–9.
Funderburgh JL, Funderburgh ML, Du Y. Stem cells in the limbal stroma. Ocul Surf. 2016;14:113–20.
Notara M, Daniels JT. Biological principals and clinical potentials of limbal epithelial stem cells. Cell Tissue Res. 2008;331:135–43.
Du Y, Funderburgh ML, Mann MM, SundarRaj N, Funderburgh JL. Multipotent stem cells in human corneal stroma. Stem Cells. 2005;23:1266–75.
Funderburgh ML, Du Y, Mann MM, SundarRaj N, Funderburgh JL. PAX6 expression identifies progenitor cells for corneal keratocytes. FASEB J: Off Publication Fed Am Soc Exp Biol. 2005;19:1371–3.
Pinnamaneni N, Funderburgh JL. Concise review: stem cells in the corneal stroma. Stem Cells. 2012;30:1059–63.
Chen Z, de Paiva CS, Luo L, Kretzer FL, Pflugfelder SC, Li DQ. Characterization of putative stem cell phenotype in human limbal epithelia. Stem Cells. 2004;22:355–66.
Ma DH, Chen HC, Lai JY, et al. Matrix revolution: molecular mechanism for inflammatory corneal neovascularization and restoration of corneal avascularity by epithelial stem cell transplantation. Ocul Surf. 2009;7:128–44.
Meek KM, Fullwood NJ. Corneal and scleral collagens--a microscopist’s perspective. Micron. 2001;32:261–72.
Abass A, Hayes S, White N, Sorensen T, Meek KM. Transverse depth-dependent changes in corneal collagen lamellar orientation and distribution. J R Soc Interface. 2015;12:20140717.
Ruberti JW, Zieske JD. Prelude to corneal tissue engineering - gaining control of collagen organization. Prog Retin Eye Res. 2008;27:549–77.
Quantock AJ, Young RD. Development of the corneal stroma, and the collagen-proteoglycan associations that help define its structure and function. Dev Dyn. 2008;237:2607–21.
Maurice DM. The structure and transparency of the cornea. J Physiol. 1957;136:263–86.
Goldman JN, Benedek GB. The relationship between morphology and transparency in the nonswelling corneal stroma of the shark. Investig Ophthalmol. 1967;6:574–600.
Benedek GB. Theory of transparency of the eye. Appl Opt. 1971;10:459–73.
Meek KM, Knupp C. Corneal structure and transparency. Prog Retin Eye Res. 2015;49:1–16.
Lewis PN, Pinali C, Young RD, Meek KM, Quantock AJ, Knupp C. Structural interactions between collagen and proteoglycans are elucidated by three-dimensional electron tomography of bovine cornea. Structure. 2010;18:239–45.
Leibowitz HM, Waring GO. Corneal disorders : clinical diagnosis and management. 2nd ed. Philadelphia: Saunders; 1998. xvi, 1172 p.
Petroll WM, Boettcher K, Barry P, Cavanagh HD, Jester JV. Quantitative assessment of anteroposterior keratocyte density in the normal rabbit cornea. Cornea. 1995;14:3–9.
Patel S, McLaren J, Hodge D, Bourne W. Normal human keratocyte density and corneal thickness measurement by using confocal microscopy in vivo. Invest Ophthalmol Vis Sci. 2001;42:333–9.
Hashmani K, Branch MJ, Sidney LE, et al. Characterization of corneal stromal stem cells with the potential for epithelial transdifferentiation. Stem Cell Res Ther. 2013;4:75.
Branch MJ, Hashmani K, Dhillon P, Jones DR, Dua HS, Hopkinson A. Mesenchymal stem cells in the human corneal limbal stroma. Invest Ophthalmol Vis Sci. 2012;53:5109–16.
Foster JW, Gouveia RM, Connon CJ. Low-glucose enhances keratocyte-characteristic phenotype from corneal stromal cells in serum-free conditions. Sci Rep. 2015;5:10839.
Chen Y, Jester JV, Anderson DM, et al. Corneal haze phenotype in Aldh3a1-null mice: in vivo confocal microscopy and tissue imaging mass spectrometry. Chem Biol Interact. 2017;276:9–14.
Jester JV. Corneal crystallins and the development of cellular transparency. Semin Cell Dev Biol. 2008;19:82–93.
Yamagami S, Usui T, Amano S, Ebihara N. Bone marrow-derived cells in mouse and human cornea. Cornea. 2005;24:S71–4.
Nakamura T, Ishikawa F, Sonoda KH, et al. Characterization and distribution of bone marrow-derived cells in mouse cornea. Invest Ophthalmol Vis Sci. 2005;46:497–503.
Takayama T, Kondo T, Kobayashi M, et al. Characteristic morphology and distribution of bone marrow derived cells in the cornea. Anat Rec (Hoboken). 2009;292:756–63.
Forrester JV, Xu H, Kuffova L, Dick AD, McMenamin PG. Dendritic cell physiology and function in the eye. Immunol Rev. 2010;234:282–304.
Saban DR. The chemokine receptor CCR7 expressed by dendritic cells: a key player in corneal and ocular surface inflammation. Ocul Surf. 2014;12:87–99.
Hattori T, Takahashi H, Dana R. Novel insights into the immunoregulatory function and localization of dendritic cells. Cornea. 2016;35(Suppl 1):S49–54.
Ellenberg D, Azar DT, Hallak JA, et al. Novel aspects of corneal angiogenic and lymphangiogenic privilege. Prog Retin Eye Res. 2010;29:208–48.
Zhong W, Montana M, Santosa SM, et al. Angiogenesis and lymphangiogenesis in corneal transplantation-a review. Surv Ophthalmol. 2018;63:453–79.
Wilson SE, Hong JW. Bowman’s layer structure and function: critical or dispensable to corneal function? A hypothesis. Cornea. 2000;19:417–20.
Beuerman RW, Pedroza L. Ultrastructure of the human cornea. Microsc Res Tech. 1996;33:320–35.
Kabosova A, Azar DT, Bannikov GA, et al. Compositional differences between infant and adult human corneal basement membranes. Invest Ophthalmol Vis Sci. 2007;48:4989–99.
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.
Weller JM, Schlotzer-Schrehardt U, Kruse FE, Tourtas T. Splitting of the recipient’s descemet membrane in descemet membrane endothelial keratoplasty-ultrastructure and clinical relevance. Am J Ophthalmol. 2016;172:1–6.
Srinivas SP. Dynamic regulation of barrier integrity of the corneal endothelium. Optom Vis Sci. 2010;87:E239–54.
He Z, Forest F, Gain P, et al. 3D map of the human corneal endothelial cell. Sci Rep. 2016;6:29047.
Worner CH, Olguin A, Ruiz-Garcia JL, Garzon-Jimenez N. Cell pattern in adult human corneal endothelium. PLoS One. 2011;6:e19483.
Harrison TA, He Z, Boggs K, Thuret G, Liu HX, Defoe DM. Corneal endothelial cells possess an elaborate multipolar shape to maximize the basolateral to apical membrane area. Mol Vis. 2016;22:31–9.
Amann J, Holley GP, Lee SB, Edelhauser HF. Increased endothelial cell density in the paracentral and peripheral regions of the human cornea. Am J Ophthalmol. 2003;135:584–90.
Barry PA, Petroll WM, Andrews PM, Cavanagh HD, Jester JV. The spatial organization of corneal endothelial cytoskeletal proteins and their relationship to the apical junctional complex. Invest Ophthalmol Vis Sci. 1995;36:1115–24.
Alaminos M, Gonzalez-Andrades M, Munoz-Avila JI, Garzon I, Sanchez-Quevedo MC, Campos A. Volumetric and ionic regulation during the in vitro development of a corneal endothelial barrier. Exp Eye Res. 2008;86:758–69.
Mergler S, Pleyer U. The human corneal endothelium: new insights into electrophysiology and ion channels. Prog Retin Eye Res. 2007;26:359–78.
Okumura N, Hirano H, Numata R, et al. Cell surface markers of functional phenotypic corneal endothelial cells. Invest Ophthalmol Vis Sci. 2014;55:7610–8.
Yoshihara M, Ohmiya H, Hara S, et al. Discovery of molecular markers to discriminate corneal endothelial cells in the human body. PLoS One. 2015;10:e0117581.
Lass JH, Gal RL, Ruedy KJ, et al. An evaluation of image quality and accuracy of eye bank measurement of donor cornea endothelial cell density in the Specular Microscopy Ancillary Study. Ophthalmology. 2005;112:431–40.
Krachmer JH, Mannis MJ, Holland EJ. Cornea. 3rd ed. Philadelphia: Elsevier/Mosby; 2011. 1–2 p.
Schroeter J, Rieck P. Endothelial evaluation in the cornea bank. Dev Ophthalmol. 2009;43:47–62.
Joyce NC. Proliferative capacity of corneal endothelial cells. Exp Eye Res. 2012;95:16–23.
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.
Hara S, Hayashi R, Soma T, et al. Identification and potential application of human corneal endothelial progenitor cells. Stem Cells Dev. 2014;23:2190–201.
Espana EM, Sun M, Birk DE. Existence of corneal endothelial slow-cycling cells. Invest Ophthalmol Vis Sci. 2015;56:3827–37.
Dirisamer M, Dapena I, Ham L, et al. Patterns of corneal endothelialization and corneal clearance after descemet membrane endothelial keratoplasty for fuchs endothelial dystrophy. Am J Ophthalmol. 2011;152:543–555 e541.
Borkar DS, Veldman P, Colby KA. Treatment of Fuchs endothelial dystrophy by Descemet stripping without endothelial keratoplasty. Cornea. 2016;35:1267–73.
Iovieno A, Neri A, Soldani AM, Adani C, Fontana L. Descemetorhexis without graft placement for the treatment of Fuchs endothelial dystrophy: preliminary results and review of the literature. Cornea. 2017;36:637–41.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2019 Springer Nature Switzerland AG
About this chapter
Cite this chapter
Gonzalez-Andrades, M., Argüeso, P., Gipson, I. (2019). Corneal Anatomy. 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_1
Download citation
DOI: https://doi.org/10.1007/978-3-030-01304-2_1
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-030-01303-5
Online ISBN: 978-3-030-01304-2
eBook Packages: MedicineMedicine (R0)