The cornea and sclera make up the outer tunic of the eye. Each is a connective tissue containing collagen fibrils embedded in a proteoglycan-rich extrafibrillar matrix, but whereas the cornea is uniquely transparent, the sclera is totally opaque. Both tissues require strength to maintain the excess pressure within the eye and to resist external knocks and the forces applied by the extraocular muscles during eye movement. This mechanical strength is provided by the deposition of collagen in a lamellar structure, where the lamellae run parallel to the surface of the tissue rather than through its thickness. The cornea is the main refractive element in the eye’s optical system, and it transmits over 90% of the incident light at visible wavelengths. Transparency is achieved because, at the nanoscopic level, the corneal collagen fibrils within the lamellae have a small, uniform diameter and are positioned with respect to each other with a high degree of lateral order. This exquisite arrangement causes destructive interference of scattered light and constructive interference of directly transmitted light throughout the visible wavelengths. As a lens, the cornea also has to be precisely curved, almost spherical near the visual axis but flattening in the periphery. Although the basis of this contour is not fully understood, corneal shape is likely achieved by the arrangement of the collagen at the microscopic level, and it is therefore not surprising that the lamellae have different preferential orientations centrally and peripherally.
The sclera (the white part of the eye) constitutes the rest of the globe. It is a tough connective tissue and is continuous with the cornea. Scleral collagen is, in composition and arrangement, more similar to that seen in skin, with wider fibrils and a much more interwoven structure than cornea. It has no optical role other than to provide a support for the retina on the back of the eye but has important physiological functions (it contains fluid outflow channels to prevent excessive pressure within the eye) and mechanical functions (it maintains eye shape during ocular movement).
This chapter describes the structure of the corneal stroma from the macroscopic level to the nanoscopic level and focuses on the role of collagen in determining the mechanical and optical properties of this fascinating connective tissue. The chapter ends with a section describing the sclera and what is currently known about the changes in collagen that accompany the development of shortsightedness (myopia).
- Tree Shrew
- Corneal Stroma
- Human Cornea
- Type Versus Collagen
- Corneal Shape
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, access via your institution.
Tax calculation will be finalised at checkout
Purchases are for personal use onlyLearn about institutional subscriptions
Unable to display preview. Download preview PDF.
Aghamohammadzadeh H, Newton RH and Meek KM (2004) X-ray scattering used to map the preferred collagen orientation in the human cornea and limbus. Structure 12. 249–256
Ameen DB, Bishop MF and McMullen T (1998) A lattice model for computing the transmissivity of the cornea and sclera. Biophys. J. 75. 2520–2531.
Atchison DA and Smith G (2000) Optics of the Human Eye. Butterworth Heinemann, Oxford, UK.
Baldock C, Gilpin CJ, Koster AJ, Ziese U, Kadler KE, Kielty CM and Holmes DF (2002) Three-dimensional reconstructions of extracellular matrix polymers using automated electron tomography. J. Struct. Biol. 138. 130–136
Benedek GB (1971) Theory of transparency of the eye. Appl. Opt. 10. 459–473.
Blochberger TC, Cornuet PK and Hassell JR (1992) Isolation and partial characterization of lumican and decorin from adult chicken corneas. A keratan sulfate-containing isoform of decorin is developmentally regulated. J Biol Chem. 267. 20613–20619.
Boote C, Dennis S, Newton RH, Puri H and Meek KM (2003) Collagen fibrils appear more closely packed in the prepupillary cornea – optical and biomechanical implications. Invest. Ophthalmol. Vis. Sci. 44. 2941–2948.
Boote C, Dennis S and Meek KM (2004) Spatial mapping of collagen fibril organisation in primate cornea – an X-ray diffraction investigation. J. Struct. Biol. 146. 359–367
Boote, C, Dennis S, Quantock AJ and Meek KM (2005) Lamellar orientation in human cornea in relation to mechanical properties. J. Struct. Biol. 149. 1–6
Boote C, Hayes S, Abahussin M and Meek KM (2006) Mapping collagen organization in the human cornea: left and right eyes are structurally distinct. Invest. Ophthalmol. Vis. Sci. 47. 901–908.
Comaish IF and Lawless MA (2002) Progressive post-LASIK kerectasia. Biomechanical instability or chronic disease process? J. Cataract Refract. Surg. 28. 2206–2213
Corpuz LM, Funderburgh JL, Funderburgh ML, Bottomly GS, Prakash S and Conrad GW (1996) Molecular cloning and tissue distribution of keratocan. Bovine corneal keratan sulphate proteoglycan 37A. J. Biol. Chem. 271. 9759–9763.
Curtin BJ, Iwamoto T and Renaldo DP (1979). Normal and staphylomatous sclera of high myopia. Arch. Ophthalmol. 97. 912–915.
Daxer A and Fratzl P (1997) Collagen fibril orientation in the human corneal stroma and its implications in keratoconus. Invest. Ophthalmol. Vis. Sci. 38. 121–129.
Daxer A, Misof K, Grabner B, Ettl A and Fratzl P (1998) Collagen fibrils in the human corneal stroma: structure and ageing. Biophys. J. 39. 644–647.
Drubaix I, Legeais J-M, Malek-Chehire N, Savoldelli M, Menasche M, Robert L, Renard G and Pouliquen Y (1996) Collagen synthesised in fluorocarbon polymer implant in the rabbit cornea. Exp. Eye Res. 62. 367–376.
ElSheikh A and Anderson K (2005) Comparative study of corneal strip extensometry and inflation tests. J. R. Soc. Interface. 2. 177–185.
Fatt I and Weisseman B (1992) Physiology of the Eye: An Introduction to the Vegitative Functions. 2nd ed. Butterworth-Heinemann, Boston.
Feuk T (1970) On the transparency of the stroma in the mammalian cornea. IEEE Trans. Biomed. Eng. BME 17. 1866–1890
Fratzl P and Daxer A (1993) Structural transformation of collagen fibrils in corneal stroma during drying. An x-ray scattering study. Biophys. J. 64. 1210–1214.
Fratzl P, Misof K, Zizak I, Rapp G, Amenitsch H and Bernstorff S (1998) Fibrillar structure and mechanical properties of collagen. J. Struct. Biol. 1122. 119–22
Freund DE, McCally RL, Farrell RA, Cristol SM, L’Hernault NL and Edelhauser HF (1995) Ultrastructure in anterior and posterior stroma of perfused human and rabbit corneas – relation to transparency. Invest. Ophthalmol. Vis. Sci. 36. 1508–1523.
Funderburgh JL, Corpuz LM, Roth MR, Funderburgh ML, Tasheva ES and Conrad GW (1997) Mimecan, the 25 KDa corneal keratan sulphate proteoglycan, is a product of the gene producing osteoglycin. J. Biol. Chem. 272, 28089–28095.
Griffith M, Osborne R, Munger R, Xiaijuan X, Doillon CJ, Laycock NLC, Hakim M, Song Y and Watsky MA (1999) Functional human corneal equivalents constructed from cell lines. Science 286. 2169–2172.
Gordon MK, Foley, JW, Linsenmayer TF and Fitch JM (1996) Temporal expression of types XII and XIV collagen mRNA and protein during avian corneal development. Dev. Dyn. 206. 49–58.
Guo X, Hutcheon, AEK, Melotti SA, Zieske JD, Trinkhaus-Randall V and Ruberti JW (2007) Morphologic characterisation of organized extracellular matrix deposition by ascorbic acid-stimulated human corneal fibroblasts. Invest. Ophthalmol. Vis. Sci. 48. 4050–4060.
Hart RW and Farrell RA (1969) Light scattering in the cornea. J. Opt. Soc. Am. 59. 766–774.
Hicks CR, Fitton JH, Chirila TV, Crawford GJ and Constable IJ (1997) Keratoprostheses: Advancing toward a true artificial cornea. Surv. Ophthalmol. 42. 175–189
Hjordtal JO (1995) Biomechanical studies of the human cornea: Development and application of a method for experimental studies of the extensibility of the intact human cornea. Acta Ophthalmol Scand 73. 364–365.
Hjortdal JO (1996) Regional elastic performance of the human cornea. J. Biomech. 29. 931–942.
Hogan MJ, Alvarado JA and Weddell J (1971) Histology of the human eye. W.B. SaundersCompany, Philadelphia.
Holmes DF, Gilpin CJ, Baldock C, Ziese,U, Koster AJ and Kadler KE (2001) Corneal collagen fibril structure in three dimensions: structural insights into fibril assembly, mechanical properties, and tissue organization. PNAS 98. 7307–7312.
Holmes DF and Kadler KE (2005) The precision of lateral size control in the assembly of corneal collagen fibrils. J. Mol. Biol. 345. 773–784.
Huang Y (1995) The effects of alkali burns and other pathological conditions on the ultrastructure of the cornea. PhD Thesis. The Open University, Milton Keynes, UK
Jester JV, Moller-Pedersen T, Huang J, Sax CM, Kays WT, Cavanagh HD, Petrol WM and Piatigorsky J (1999) The cellular basis of corneal transparency: evidence for “corneal crystallins”. J. Cell Sci. 112. 613–622.
Johnson CS, Mian SI, Moroi S, Epstein D, Izatt J and Afshari NA (2007) Role of corneal elasticity in damping intraocular pressure. Invest. Ophthalmol. Vis. Sci. 48. 2540–2544.
Jue B and Maurice DM (1986) The mechanical properties of the rabbit and human cornea. J. Biomech. 19. 847–853
Kirby MC, Aspden RM and Hukins DWL (1988) Determination of the orientation distribution function for collagen fibrils in a connective tissue site from a high-angle x-ray diffractin pattern. J. Appl. Cryst. 21. 929–934.
Kokott W (1938) Ubermechanisch-funktionelle Strikturen des Auges. Albrecht von Graefes. Arch. Ophthalmol. 138. 424–485.
Komai Y and Ushiki T (1991) The three-dimensional organisation of collagen fibrils in the human cornea and sclera. Invest. Ophthalmol. Vis. Sci. 32. 2244–2258.
Leonard DW and Meek KM (1997). Estimation of the refractive indices of collagen fibrils and ground substance of the corneal stroma using data from X-ray diffraction. Biophys. J. 72. 1382–1387
Li Y, Vergnes JP, Cornuet PK and Hassell JR (1992) cDNA clone to chick corneal chondroitin/dermatan sulfate proteoglycan reveals identity of decorin. Arch. Biochem. Biophys. 296. 190–197.
Linsenmayer TF, Gibney E, Igoe F, Gordon MK, Fitch JM, Fessler LI and Birk DE (1993) Type V collagen: Molecular structure and fibrillar organization of the chicken \UPalpha1(V) NH_2-terminal domain, a putative regulator of corneal fibrillogenesis. J. Cell Biol. 121. 1181–1189
Marshall GE, Konstas AG and Lee WR (1991) Immunogold fine structural localization of extracellular matrix components in aged human cornea. I. Types I-IV collagen and laminin. Graefes Arch. Clin. Exp. Ophthalmol. 229. 157–163.
Maurice DM (1957) The structure and transparency of the cornea. J. Physiol. 136. 263–286.
Maurice DM (1969) The cornea and sclera. In Davson H ed. The Eye, Academic Press, New York. pp. 489–599.
McBrien NA, Cornell LM and Gentle A (2001) Structural and ultrastructural changes in the sclera in a mammalian model of high myopia. Invest. Ophthalmol. Vis. Sci. 42. 2179–2187.
McBrien NA and Gentle A (2003) Role of sclera in the development and pathological complications of myopia. Prog. Ret. Eye Res. 22. 307–338.
McMonnies CW and Schief WK (2006) Biomechanically coupled curvature transfer in normal and keratoconus corneal collagen. Eye Contact Lens. 32. 51–62.
Meek KM and Holmes DF (1983) Interpretation of the electron microscopical appearance of collagen fibrils from corneal stroma. Int. J. Biol. Macromol. 5. 17–25
Meek KM, Blamires T, Elliott GF, Gyi T and Nave C (1987). The organisation of collagen fibrils in the human corneal stroma: A synchrotron X-ray diffraction study. Current Eye Res. 6, 841–846.
Meek KM and Fullwood NJ (2001) Corneal and scleral collagens – a microscopist’s perspective. Micron 32. 261–272.
Meek KM, Fullwood NJ, Cooke PH, Elliott GF, Maurice DM, Quantock AJ, Wall RS and Worthington CR (1991) Synchrotron X-ray diffraction studies of the cornea with implications for stromal hydration. Biophys. J. 60. 467–474
Meek KM and Leonard DW (1993) Ultrastructure of the corneal stroma – a comparative study. Biophys. J. 64. 273–280.
Meek KM, Leonard DW, Connon C, Dennis S and Khan S (2003) Transparency, swelling and scarring in the corneal stroma. Eye 17. 927–936.
Meek KM and Boote C (2004) The organization of collagen in the corneal stroma. Exp. Eye Res. 78. 503–512.
Meek KM, Tuft SJ, Huang Y, Gill P, Hayes S., Newton RH and Bron AJ. (2005) Changes in collagen orientation and distribution in keratoconus corneas. Invest. Ophthalmol. Vis. Sci. 46. 1948–1956.
Morishige N, Petroll WM, Nishida T, Kenney MC and Jester JV (2006) Non-invasive stromal collagen imaging using two-photon-generated second-harmonic signals. J Cataract Refract. Surg. 32. 1784–1791.
Muller LJ, Pels E and Vrensen GFJM (2001) The specific architecture of the anterior stroma accounts for maintenance of corneal curvature. Br. J. Ophthalmol. 85. 437–443.
Nakao H, Matsuda T, Nakayama Y, Hara Y and Saishin M (1993) Design concept and construction of a hybrid lamellar keratoprosthesis. ASAIO J. 39. M257–M260
Newsome DA, Foidart JM, Hassell JR, Krachmer JH, Rodrigues MM and Katz SI (1981) Detection of specific collagen types in normal and keratoconus corneas. Invest. Ophthalmol. Vis. Sci. 20. 738–750.
Olsen TW, Aaberg SY, Geroski DH and Edelhauser HF (1998) Human sclera: thickness and surface area. Am. J. Ophthalmol. 125. 237–241.
Parry DAD and Craig AS (1988) Collagen fibrils during development and maturation and their contribution to the mechanical attributes of connective tissue. In Nimni ME, ed. Collagen: biochemistry, biomechanics, biotechnology. CRC Press, Boca Raton. Vol. II pp 1–40.
Polack FM (1961) Morphology of the cornea. Am. J. Ophthalmol. 51. 179–184.
Quantock AJ, Dennis S, Adachi W, Kinoshita S, Boote C, Meek KM, Matsushima Y, Tachibana M. (2003) Annulus of collagen fibrils in mouse cornea and structural matrix alterations in a murine-specific keratopathy. Invest. Ophthalmol. Vis. Sci. 44. 1906.
Rada JA, Achen VR, Perry CA and Fox PW (1997) Proteoglycans in the human sclera. Evidence for the presence of aggrecan. Invest. Ophthalmol. Vis. Sci. 38. 1740–1751
Rada JA, Achen VR, Penugonda S, Schmidt RW and Mount BA (2000) Proteoglycan composition in the human sclera during growth and aging. Invest. Ophthalmol. Vis. Sci. 41. 1639–1648
Ricard-Blum S and Ruggiero F (2005) The collagen superfamily: from the extracellular matrix to the cell membrane. Pathol. Biol. 53. 430–442.
Ruberti JW, Zieske JD and Trinkaus-Randall V (2007) Corneal-tissue replacement. In Lanza RP, Langer R, and Vacanti J eds. Principles of Tissue Engineering 3^rd Ed. () Elsevier, Inc, New York.
Rucklidge GJ, Milne G, McGaw BA, Milne E and Robins SP (1992) Turnover rates of different collagen types measured by isotope ratio mass spectrometry. Biochim. Biophys. Acta 1156. 57–61.
Sayers Z, Whitburn SB, Koch MHJ, Meek KM and Elliott GF (1982). Synchrotron X-ray diffraction study of corneal stroma. J. Mol. Biol. 160. 593–607.
Scott JE and Haigh M (1985) ‘Small’-proteoglycan:collagen interactions: keratan sulphate proteoglycan associates with rabbit corneal collagen fibrils at the ‘a’ and ‘c’ bands. Biosci. Rep. 5. 765–774
Siegwart JT and Norton TT (1999) Regulation of the mechanical properties of the tree shrew sclera by the visual environment. Vision Res. 39. 387–407
Sjontoft E and Edmund C (1987) In vivo determination of Young’s modulus for the human cornea. Bull. Math. Biol. 49. 217–232.
Smolek MK (1993) Interlamellar cohesive strength in the vertical meridian of human eye bank corneas. Invest. Ophthalmol. Vis. Sci. 34. 2962–2969.
Soriano ES, Campos MS and Michelacci YM (2000) Effect of epithelial debridement on glycosaminoglycan synthesis by human corneal explants. Clinica. Chemica. Acta. 295. 41–62.
Torbet J, Malbouyres M, Builles N, Justin V, Roulet M, Damour O, Oldberg A, Ruggiero F and Hulmes DJS (2007) Orthogonal scaffold of magnetically aligned collagen lamellae for corneal stromal reconstruction. Biomaterials 28. 4268–4276
Twersky V (1975) Transparency of pair-correlated, random distributions of small scatterers, with applications to the cornea. J. Opt. Soc. Am. 65. 524–530.
Watson PG and Young RD (2004) Scleral structure, organisation and disease. A review. Exp. Eye Res. 78. 609–623.
Wessel H, Anderson S, Fite D, Halvas E, Hempel J and SundarRaj N (1997) Type XII collagen contributes to diversities in human corneal and limbal extracellular matrices. Invest. Ophthalmol. Vis. Sci. 38. 2408–2422.
Wollensak G, Sporl E and Seiler T (2003) Behandlung von Keratokonus durch kollagenvernetzung. Ophthalmologe 100. 44–49
Yamauchi M, Chandler GS, Tanzawa H and Katz EP (1996) Cross-linking and the molecular packing of corneal collagen. Biochem. Biophys. Res. Comm. 219. 311–315.
Editors and Affiliations
© 2008 Springer Science+Business Media, LLC
About this chapter
Cite this chapter
Meek, K. (2008). The Cornea and Sclera. In: Fratzl, P. (eds) Collagen. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-73906-9_13
Publisher Name: Springer, Boston, MA
Print ISBN: 978-0-387-73905-2
Online ISBN: 978-0-387-73906-9