Wu, J.J. and Wu, W. and Tholozan, F.M. and Saunter, C.D. and Girkin, J.M. and Quinlan, R.A. (2015) 'A dimensionless ordered pull-through model of the mammalian lens epithelium evidences scaling across species and explains the age-dependent changes in cell density in the human lens.', Journal of the Royal Society interface., 12 (108). p. 20150391.
We present a mathematical (ordered pull-through; OPT) model of the cell-density profile for the mammalian lens epithelium together with new experimental data. The model is based upon dimensionless parameters, an important criterion for inter-species comparisons where lens sizes can vary greatly (e.g. bovine (approx. 18 mm); mouse (approx. 2 mm)) and confirms that mammalian lenses scale with size. The validated model includes two parameters: β/α, which is the ratio of the proliferation rate in the peripheral and in the central region of the lens; and γGZ, a dimensionless pull-through parameter that accounts for the cell transition and exit from the epithelium into the lens body. Best-fit values were determined for mouse, rat, rabbit, bovine and human lens epithelia. The OPT model accounts for the peak in cell density at the periphery of the lens epithelium, a region where cell proliferation is concentrated and reaches a maximum coincident with the germinative zone. The β/α ratio correlates with the measured FGF-2 gradient, a morphogen critical to lens cell survival, proliferation and differentiation. As proliferation declines with age, the OPT model predicted age-dependent changes in cell-density profiles, which we observed in mouse and human lenses.
|Keywords:||Eye lens, Cell proliferation, Ageing, Cataract, Mathematical model, Scaling.|
|Full text:||(VoR) Version of Record|
Available under License - Creative Commons Attribution.
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|Publisher Web site:||http://dx.doi.org/10.1098/rsif.2015.0391|
|Publisher statement:||© 2015 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.|
|Date accepted:||28 May 2015|
|Date deposited:||19 November 2015|
|Date of first online publication:||06 July 2015|
|Date first made open access:||No date available|
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