September 2016
Volume 57, Issue 12
ARVO Annual Meeting Abstract  |   September 2016
Collagen-Proteoglycan Interactions in the Corneal Stroma: A Computer Simulation
Author Affiliations & Notes
  • Carlo Knupp
    Cardiff University, Cardiff, United Kingdom
  • Rob D Young
    Cardiff University, Cardiff, United Kingdom
  • Andrew J Quantock
    Cardiff University, Cardiff, United Kingdom
  • Keith M Meek
    Cardiff University, Cardiff, United Kingdom
  • Footnotes
    Commercial Relationships   Carlo Knupp, None; Rob Young, None; Andrew Quantock, None; Keith Meek, None
  • Footnotes
    Support  MRC Grant MR/K000837/1
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 2362. doi:
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      Carlo Knupp, Rob D Young, Andrew J Quantock, Keith M Meek; Collagen-Proteoglycan Interactions in the Corneal Stroma: A Computer Simulation. Invest. Ophthalmol. Vis. Sci. 2016;57(12):2362.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose : Recent three-dimensional electron microscopy studies carried out by our group (e.g. Lewis et al, Structure,18, 1-7, 2010) confirmed that the spatial distribution of collagen fibrils in the corneal stroma is regulated by the interaction of proteoglycans with the collagen fibrils. From these studies, we suggested that the relatively flexible proteoglycan chains make temporally transient links between adjacent collagen fibrils in a non-systematic, asymmetric way and that they give rise to forces that are ultimately responsible for the spatial distribution of the collagen fibrils in the cornea. Our purpose is to simulate these interactions computationally and verify whether they can explain the most salient structural and functional characteristics of the cornea.

Methods : Ad-hoc software was written to simulate the behaviour of the collagen fibrils under the influence of external forces brought about by the action of the proteoglycans.

Results : Our computer simulation covers a 1 second-long time-dependent evolution of a portion of the corneal stroma (with up to 1000 fibrils) in which the collagen fibrils are subject to thermal motion and proteoglycan induced forces. The appearance of the simulated corneas is remarkably similar to what is seen in electron micrographs, as confirmed by the calculation of Fourier transforms and radial projection functions for the simulations and the micrographs. The calculation of transparency and X-ray diffraction patterns from the simulated corneas are also in good agreement with the data collected from real corneas. In addition, we have probed the possibility of other proteoglycan unrelated forces acting on the collagen fibrils, such as the pressure exercised by adjacent corneal lamellae, which shows that they may contribute substantially to the overall collagen fibril distribution in the cornea.

Conclusions : The fibril distributions obtained in our simulations compare favourably with electron microscopical, X-ray diffraction and corneal transparency data, indicating that the local interactions between collagen and proteoglycans can explain some of the main structural and functional aspects of the cornea.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.


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