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Quantification of collagen ultrastructure after penetrating keratoplasty – implications for corneal biomechanics

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Boote, Craig, Dooley, Erin P., Gardner, Steven J., Kamma-Lorger, Christina S., Hayes, Sally, Nielsen, Kim, Hjortdal, Jesper, Sorensen, Thomas +2 more·2013·PLoS ONE
DOI 10.1371/journal.pone.0068166PMC PMC3702563
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Abstract

PURPOSE: To quantify long-term changes in stromal collagen ultrastructure following penetrating keratoplasty (PK), and evaluate their possible implications for corneal biomechanics. METHODS: A pair of 16 mm post-mortem corneo-scleral buttons was obtained from a patient receiving bilateral penetrating keratoplasty 12 (left)/28 (right) years previously. Small-angle x-ray scattering quantified collagen fibril spacing, diameter and spatial order at 0.5 mm or 0.25 mm intervals along linear scans across the graft margin. Corresponding control data was collected from two corneo-scleral buttons with no history of refractive surgery. Wide-angle x-ray scattering quantified collagen fibril orientation at 0.25 mm (horizontal)×0.25 mm (vertical) intervals across both PK specimens. Quantification of orientation changes in the graft margin were verified by equivalent analysis of data from a 13 year post-operative right PK specimen obtained from a second patient in a previous study, and comparison made with new and published data from normal corneas. RESULTS: Marked changes to normal fibril alignment, in favour of tangentially oriented collagen, were observed around the entire graft margin in all PK specimens. The total number of meridional fibrils in the wound margin was observed to decrease by up to 40%, with the number of tangentially oriented fibrils increasing by up to 46%. As a result, in some locations the number of fibrils aligned parallel to the wound outnumbered those spanning it by up to five times. Localised increases in fibril spacing and diameter, with an accompanying reduction in matrix order, were also evident. CONCLUSIONS: Abnormal collagen fibril size and spatial order within the PK graft margin are indicative of incomplete stromal wound remodelling and the long term persistence of fibrotic scar tissue. Lasting changes in collagen fibril orientation in and around PK wounds may alter corneal biomechanics and compromise the integrity of the graft-host interface in the long term.

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Crossref · 10.1371/journal.pone.0068166

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  • The opacity of corneal scars is a result of improper remodelling of the connective tissue matrix; collagen fibrils are wider than normal and poorly ordered in scar tissue.

    “On the other hand, the opacity of corneal scars is a result of improper remodelling of the connective tissue matrix; collagen fibrils are wider than normal and poorly ordered in scar tissue (Boote et al., 2013).”

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

    The Results (Collagen Spatial Organisation) report locally increased fibril diameter and reduced spatial order at the graft margins compared with unwounded corneas. The Discussion links these changes to incomplete remodelling and fibrotic scar tissue, but says they *could be a contributing factor* to visible opacity. The claim states a definite cause for corneal scars generally, beyond what the paper establishes for these graft margins. (LLM, conf=0.88)

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Research works printed but not linked: 36

  1. [1]Meek KM (2009) Corneal collagen–its role in maintaining corneal shape and transparency. Biophysical Reviews 1: 83– 93. 28509987 PMC5425665
  2. [2]Connon CJ, Meek K (2003) Organization of corneal collagen fibrils during the healing of trephined wounds in rabbits. Wound Repair Regen 11: 71– 78. 12581429
  3. [3]Hayes S, Young R, Boote C, Hawksworth N, Huang Y, et al (2010) A structural investigation of corneal graft failure in suspected recurrent keratoconus. Eye 24: 728– 734. 19575034
  4. [4]Kamma-Lorger CS, Hayes S, Boote C, Burghammer M, Boulton ME, et al (2009) Effects on collagen orientation in the cornea after trephine injury. Molecular Vision 15: 378– 385. 19234631 PMC2645905
  5. [5]Cintron C, Schneider H, Kublin C (1973) Corneal scar formation. Exp Eye Res 17: 251– 259. 4271803
  6. [6]Rawe IM, Meek KM, Leonard DW, Takahashi T, Cintron C (1994) Structure of corneal scar tissue: an X-ray diffraction study. Biophys J 67: 1743– 1748. 7819506 PMC1225536
  7. [7]Kamma-Lorger CS, Boote C, Hayes S, Albon J, Boulton ME, et al (2009) Collagen ultrastructural changes during stromal wound healing in organ cultured bovine corneas. Experimental Eye Research 88: 953– 959. 19133259
  8. [8]Dawson DG, Edelhauser HF, Grossniklaus HE (2005) Long-term histopathologic findings in human corneal wounds after refractive surgical procedures. Am J Ophthalmol 139: 168– 178. 15652843
  9. [9]Melles GR, Binder PS (1990) A comparison of wound healing in sutured and unsutured corneal wounds. Arch Ophthalmol 108: 1460– 1469. 2222279
  10. [10]Steele C (2009) Corneal wound healing: a review. Optometry Today 24: 28– 32.
  11. [11]Farley MK, Pettit TH (1987) Traumatic wound dehiscence after penetrating keratoplasty. Am J Ophthalmol 104: 44– 49. 3300352
  12. [12]Lang GK, Green WR, Maumenee AE (1986) Clinicopathologic studies of keratoplasty eyes obtained post mortem. Am J Ophthalmol 101: 28– 40. 3510548
  13. [13]Morrison JC, Swan KC (1982) Full-thickness lamellar keratoplasty. A histologic study in human eyes. Ophthalmology 89: 715– 719. 6750493
  14. [14]Morrison JC, Swan KC (1982) Bowman's layer in penetrating keratoplasties of the human eye. Arch Ophthalmol 100: 1835– 1838. 6753806
  15. [15]Morrison JC, Swan KC (1983) Descemet's membrane in penetrating keratoplasties of the human eye. Arch Ophthalmol 101: 1927– 1929. 6360112
  16. [16]Boote C, Hayes S, Abahussin M, Meek KM (2006) Mapping collagen organisation in the human cornea: left and right eyes are structurally distinct. Invest Ophthalmol Vis Sci 47: 901– 908. 16505022
  17. [17]Meek KM, Quantock AJ (2001) The use of X-ray scattering techniques to determine corneal ultrastructure. Prog Retin Eye Res 20: 95– 137. 11070369
  18. [18]Boote C, Dennis S, Newton RH, Puri H, Meek KM (2003) Collagen fibrils appear more closely packed in the prepupilliary cornea- optical and biomechanical implications. Investigative Ophthalmology and Visual Science 44: 2941– 2948. 12824235
  19. [19]Meek K, Quantock AJ, Boote C, Liu CY, Kao WWY (2003) An X-ray scattering investigation of corneal structure in keratocan deficient mice. Matrix Biology 22: 467– 475. 14667839
  20. [20]Boote C, Du Y, Morgan SR, Harris J, Kamma-Lorger CS, et al (2012) Quantitative Assessment of Ultrastructure and Light Scatter in Mouse Corneal Debridement Wounds. Invest Ophthalmol Vis Sci 53: 2786– 2795. 22467580 PMC3367468
  21. [21]Meek KM, Boote C (2009) The use of x-ray scattering techniques to quantify the orientation and distribution of collagen in the corneal stroma. Prog Retin Eye Res 28: 369– 392. 19577657
  22. [22]Borcherding MS, Blacik LJ, Sittig RA, Bizzel JW, Breen M, et al (1975) Proteoglycans and Collagen Fibre Organisation in Human Corneoscleral Tissue. Experimental Eye Research 21: 59– 70. 124659
  23. [23]Boote C, Kamma-Lorger CS, Hayes S, Harris J, Burghammer M, et al (2011) Quantification of collagen organization in the peripheral human cornea at micron-scale resolution. Biophys J 101: 33– 42. 21723812 PMC3127175
  24. [25]Boote C, Dennis S, Huang Y, Meek K (2005) Lamellar orientation in human cornea in relation to mechanical properties. Journal of Structural Biology 149: 1– 6. 15629652
  25. [26]Daxer A, Fratzl P (1997) Collagen fibril orientation in the human corneal stroma and its implications in keratoconus. Investigative Ophthalmology and Visual Science 38: 121– 129. 9008637
  26. [27]Pramanik S, Musch DC, Sutphin JE, Farjo AA (2006) Extended long-term outcomes of penetrating keratoplasty for keratoconus. Ophthalmology 113: 1633– 1638. 16828503
  27. [28]Calkins JL, Hochheimer BF, Stark WJ (1981) Corneal wound healing: holographic stress-test analysis. Invest Ophthalmol Vis Sci 21: 322– 334. 7019152
  28. [29]Pettinelli DJ, Starr CE, Stark WJ (2005) Late traumatic corneal wound dehiscence after penetrating keratoplasty. Arch Ophthalmol 123: 853– 856. 15955989
  29. [30]Vrana E, Builles N, Hindie M, Damour O, Aydinli A, et al (2008) Contact guidance enhances the quality of a tissue engineered corneal stroma. J Biomed Mater Res A 84: 454– 463. 17618494
  30. [31]Boyce BL, Grazier JM, Jones RE, Nguyen TD (2008) Full-field deformation of bovine cornea under constrained inflation conditions. Biomaterials 4: 4. 18603294
  31. [32]Farrell RA, McCally RL (2000) Corneal Transparency. In: Albert DM, Jakobiec FA, editors. Principles and Practice of Ophthalmology. Philadelphia: W.B. Saunders Company. 629–643.
  32. [33]Abahussin M, Hayes S, Knox Cartwright NE, Kamma-Lorger CS, Khan Y, et al (2009) 3D collagen orientation study of the human cornea using X-ray diffraction and femtosecond laser technology. Invest Ophthalmol Vis Sci 50: 5159– 5164. 19516010
  33. [34]Meek KM, Newton RH (1999) Organization of collagen fibrils in the corneal stroma in relation to mechanical properties and surgical practice. Journal of Refractive Surgery 15: 695– 699. 10590012
  34. [35]Smelser GK, Polack FM, Ozanics V (1965) Persistence of donor collagen in corneal transplants. Exp Eye Res 4: 349– 354. 5325830
  35. [36]Nguyen TD, Boyce BL (2011) An inverse finite element method for determining the anisotropic properties of the cornea. Biomech Model Mechanobiol 10: 323– 337. 20602142
  36. [37]Sen DK, Mohan H, Gupta DK (1969) Bilateral peripheral sclero-cornea. Acta Ophthalmol (Copenh) 47: 1041– 1043. 5394837

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Authors
Boote, C., Dooley, E. P., Gardner, S. J., Kamma-Lorger, C. S., Hayes, S., Nielsen, K., Hjortdal, J., Sorensen, T., Terrill, N. J., & Meek, K. M.
Affiliations
  • Cardiff University (GB)
  • Aarhus University Hospital (DK)
  • Diamond Light Source (GB)
Corresponding author
Meek, Keith M.
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2013-07-05
Volume
8
Issue
7
Pages
e68166
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0068166
PMC
PMC3702563
OpenAlex
W1971024475
Cited by
21
References
1
Citations by year
2025: 1 · 2024: 4 · 2023: 2 · 2019: 3 · 2017: 1 · 2016: 5 · 2015: 4 · 2014: 1
FWCI
2.37
Type
journal article
Language
en
Update notices
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • ORCA Online Research @Cardiff (Cardiff University) (acceptedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Medical Research Council (MR/K000837/1, G0600755)
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 › Ophthalmology › Ocular Infections and Treatments
Keywords
penetrating keratoplasty, collagen ultrastructure, corneal stroma, collagen fibril orientation, corneal biomechanics, graft-host interface, corneal fibrosis, small-angle X-ray scattering, wide-angle X-ray scattering
MeSH terms
Aged, Collagen, Cornea, Corneal Stroma, Humans, Middle Aged, Tissue Donors, X-Ray Diffraction, Keratoplasty, Penetrating

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