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Cited by 152Corneal surgery and disordersCorneal Surgery and TreatmentsOcular Surface and Contact Lens

Three-dimensional distribution of transverse collagen fibers in the anterior human corneal stroma

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Winkler, Moritz, Shoa, Golroxan, Xie, Yilu, Petsche, Steven J., Pinsky, Peter M., Juhasz, Tibor, Brown, Donald J., Jester, James V.·2013·Investigative Opthalmology & Visual Science
DOI 10.1167/iovs.13-13150PMC PMC4589141
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Abstract

PURPOSE: Recent investigations of human corneal structure and biomechanics have shown that stromal collagen fibers (lamellae) are organized into a complex, highly intertwined three-dimensional meshwork of transverse oriented fibers that increases stromal stiffness and controls corneal shape. The purpose of this study was to characterize the three-dimensional distribution of transverse collagen fibers along the major meridians of the cornea using an automated method to rapidly quantify the collagen fibers' angular orientation. METHODS: Three eyes from three donors were perfusion-fixed under pressure, excised, and cut into four quadrants. Quadrants were physically sectioned using a vibratome and scanned using nonlinear optical high-resolution macroscopy. Planes were analyzed numerically using software to identify collagen fiber angles relative to the corneal surface, stromal depth, and radial position within the anterior 250 μm of the stroma. RESULTS: The range of fiber angles and the fiber percentage having an angular displacement greater than ±3.5° relative to the corneal surface ("transverse fibers") was highest in the anterior stroma and decreased with depth. Numerical analysis showed no significant differences in fiber angles and transverse fibers between quadrants, meridians, and radial position. CONCLUSIONS: These results match our previous observation of a depth-dependent gradient in stromal collagen interconnectivity in the central cornea, and show that this gradient extends from the central cornea to the limbus. The lack of a preferred distribution of angled fibers with regard to corneal quadrant or radial position likely serves to evenly distribute loads and to avoid the formation of areas of stress concentration.

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  • The bow spring-like arrangement of anterior lamellae provides structural support to maintain the shape of the anterior corneal surface.

    “and that this bow spring-like arrangement provides structural support to maintain the shape of the anterior corneal surface (Winkler et al., 2013).”

    From Corneal structure and transparency (2015) · cites this paper as Winkler et al., 2013

    The Discussion says that interconnected transverse fibers in the anterior stroma likely stabilize corneal shape. It does not describe the anterior lamellae as a bow spring-like arrangement or establish that specific arrangement as the mechanism supporting the anterior surface. (LLM, conf=0.82)

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Research works printed but not linked: 32

  1. [1]1. Meek KM, Boote C. The use of x-ray scattering techniques to quantify the orientation and distribution of collagen in the corneal stroma. Prog Retin Eye Res . 2009;28:369-392.
  2. [2]2. Daxer A, Misof K, Grabner B, Ettl A, Fratzl P . Collagen fibrils in the human corneal stroma: structure and aging. Invest Ophthalmol Vis Sci . 1998;39:644-648.
  3. [3]3. Quantock AJ, Young RD. Development of the corneal stroma, and the collagen-proteoglycan associations that help define its structure and function. Dev Dyn . 2008;237:2607-2621.
  4. [4]4. Abahussin M, Hayes S, Cartwright NEK, et al. 3D collagen orientation study of the human cornea using x-ray diffraction and femtosecond laser technology. Invest Ophthalmol Vis Sci . 2009;50:5159-5164.
  5. [6]6. Meek KM, Boote C. The organization of collagen in the corneal stroma. Exp Eye Res . 2004;78:503-512.
  6. [7]7. Morishige N, Petroll WM, Nishida T, Kenney MC, Jester JV . Noninvasive corneal stromal collagen imaging using twophoton-generated second-harmonic signals. J Cataract Refract Surg . 2006;32:1784.
  7. [8]8. Morishige N, Wahlert AJ, Kenney MC, et al. Second-harmonic imaging microscopy of normal human and keratoconus cornea. Invest Ophthalmol Vis Sci . 2007;48:1087-1094.
  8. [9]9. Komai Y, Ushiki T. The three-dimensional organization of collagen fibrils in the human cornea and sclera. Invest Ophthalmol Vis Sci . 1991;32:2244-2258.
  9. [10]10. Boote C, Hayes S, Abahussin M, Meek KM. Mapping collagen organization in the human cornea: left and right eyes are structurally distinct. Invest Ophthalmol Vis Sci . 2006;47:901908.
  10. [11]11. Borcherding MS, Blacik L, Sittig R, Bizzell JW, Breen M, Weinstein H. Proteoglycans and collagen fibre organization in human corneoscleral tissue. Exp Eye Res . 1975;21:59-70.
  11. [12]12. Konomi H, Hayashi T, Nakayasu K, Arima M. Localization of type V collagen and type IV collagen in human cornea, lung, and skin. Immunohistochemical evidence by anti-collagen antibodies characterized by immunoelectroblotting. Am J Pathol . 1984;116:417.
  12. [13]13. Stanworth A, Naylor E. Polarized light studies of the cornea I. The isolated cornea. J Exp Biol . 1953;30:160-163.
  13. [14]14. Hahnel C, Somodi S, Weiss DG, Guthoff RF . The keratocyte network of human cornea: a three-dimensional study using confocal laser scanning fluorescence microscopy. Cornea . 2000;19:185.
  14. [15]15. Jalbert I, Stapleton F , Papas E, Sweeney D, Coroneo M. In vivo confocal microscopy of the human cornea. Br J Ophthalmol . 2003;87:225-236.
  15. [16]16. Han M, Giese G, Bille J. Second harmonic generation imaging of collagen fibrils in cornea and sclera. Opt Express . 2005;13: 5791-5797.
  16. [17]17. Jester JV , Winkler M, Jester BE, Nien C, Chai D, Brown DJ. Evaluating corneal collagen organization using high-resolution nonlinear optical macroscopy. Eye Contact Lens . 2010;36: 260-264.
  17. [18]18. Winkler M, Jester BE, Nien-Shy C, Chai D, Brown DJ, Jester JV . High resolution macroscopy (HRMac) of the eye using nonlinear optical imaging. Proc SPIE . 2010;7589:758906.
  18. [19]19. Winkler M, Chai D, Kriling S, et al. Nonlinear optical macroscopic assessment of 3-D corneal collagen organization and axial biomechanics. Invest Ophthalmol Vis Sci . 2011;52: 8818-8827.
  19. [20]20. Petsche SJ, Chernyak D, Martiz J, Levenston ME, Pinsky PM. Depth-dependent transverse shear properties of the human corneal stroma. Invest Ophthalmol Vis Sci . 2012;53:873-880.
  20. [21]21. Schindelin J, Arganda-Carreras I, Frise E, et al. Fiji: an opensource platform for biological-image analysis. Nature Methods . 2012;9:676-682.
  21. [22]22. Rezakhaniha R, Agianniotis A, Schrauwen JT, et al. Experimental investigation of collagen waviness and orientation in the arterial adventitia using confocal laser scanning microscopy. Biomech Model Mechanobiol . 2012;11:461-473.
  22. [23]23. M¨ uller LJ, Pels E, Vrensen GF . The specific architecture of the anterior stroma accounts for maintenance of corneal curvature. Br J Ophthalmol . 2001;85:437-443.
  23. [24]24. Quantock AJ, Boote C, Young RD, et al. Small-angle fibre diffraction studies of corneal matrix structure: a depth-profiled investigation of the human eye-bank cornea. J Appl Crystallogr . 2007;40:335-340.
  24. [25]25. Meek KM, Tuft SJ, Huang Y, et al. Changes in collagen orientation and distribution in keratoconus corneas. Invest Ophthalmol Vis Sci . 2005;46:1948-1956.
  25. [26]26. McMonnies CW. Mechanisms of rubbing-related corneal trauma in keratoconus. Cornea . 2009;28:607-615.
  26. [27]27. Tan H-Y, Sun Y, Lo W, et al. Multiphoton fluorescence and second harmonic generation imaging of the structural alterations in keratoconus ex vivo. Invest Ophthalmol Vis Sci . 2006;47:5251-5259.
  27. [28]28. Elsheikh A, Wang D, Brown M, Rama P , Campanelli M, Pye D. Assessment of corneal biomechanical properties and their variation with age. Curr Eye Res . 2007;32:11-19.
  28. [29]29. Pinsky PM, van der Heide D, Chernyak D. Computational modeling of mechanical anisotropy in the cornea and sclera. J Cataract Refract Surg . 2005;31:136-145.
  29. [30]30. Grytz R, Meschke G. A computational remodeling approach to predict the physiological architecture of the collagen fibril network in corneo-scleral shells. Biomech Model Mechanobiol . 2010;9:225-235.
  30. [31]31. Studer H, Larrea X, Riedwyl H, B¨ uchler P. Biomechanical model of human cornea based on stromal microstructure. J Biomech . 2010;43:836-842.
  31. [32]32. Holzapfel GA. Three-dimensional modeling and computational analysis of the human cornea considering distributed collagen fibril orientations. J Biomech Eng . 2008;130:061006-061001.
  32. [33]33. Sondergaard AP , Ivarsen A, Hjortdal J. Reduction of stromal swelling pressure after UVA-riboflavin cross-linking. Invest Ophthalmol Vis Sci . 2013;54:1625-1634.

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Authors
Winkler, M., Shoa, G., Xie, Y., Petsche, S. J., Pinsky, P. M., Juhasz, T., Brown, D. J., & Jester, J. V.
Affiliations
  • University of California, Irvine (US)
  • Stanford University (US)
  • Department of Biomedical Engineering, University of California, Irvine, California 2Gavin Herbert Eye Institute, University of California, Irvine, California
Corresponding author
Jester, James V.
ORCID
Venue
Investigative Opthalmology & Visual Science
Publisher
Association for Research in Vision and Ophthalmology (ARVO)
Published
2013-11-05
Volume
54
Issue
12
Pages
7293
ISSN
  • 0146-0404 (ISSN-L)
  • 1552-5783
DOI
10.1167/iovs.13-13150
PMC
PMC4589141
OpenAlex
W2328742974
Cited by
152
References
1
Citations by year
2026: 4 · 2025: 16 · 2024: 10 · 2023: 11 · 2022: 15 · 2021: 8 · 2020: 8 · 2019: 13 · 2018: 11 · 2017: 15 · 2016: 14 · 2015: 20 · 2014: 7
FWCI
9.73
Type
journal article
Language
en
Open access
Locations
  • Investigative Ophthalmology & Visual Science (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • Research to Prevent Blindness
  • Discovery Eye Foundation
  • Ögonfonden
  • National Institutes of Health
  • National Eye Institute (EY018665, R01EY019719, R01EY018665, EY019719)
Topics
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Corneal surgery and disorders
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Corneal Surgery and Treatments
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Ocular Surface and Contact Lens
Keywords
corneal stroma, collagen fiber orientation, anterior cornea, limbus, corneal biomechanics, corneal stiffness
MeSH terms
Aged, Aged, 80 and over, Analysis of Variance, Autopsy, Collagen, Corneal Stroma, Humans, Middle Aged

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