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

Wu, J.J.; Wu, W.; Tholozan, F.M.; Saunter, C.D.; Girkin, J.M.; Quinlan, R.A.

Abstract

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.

Citation

Wu, J., Wu, W., Tholozan, F., Saunter, C., Girkin, J., & Quinlan, R. (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), https://doi.org/10.1098/rsif.2015.0391

• Journal Article Type: Article
• Acceptance Date: May 28, 2015
• Online Publication Date: Jul 6, 2015
• Publication Date: Jul 1, 2015
• Deposit Date: Nov 18, 2015
• Publicly Available Date: Nov 19, 2015
• Journal: Journal of the Royal Society, Interface
• Print ISSN: 1742-5689
• Electronic ISSN: 1742-5662
• Publisher: The Royal Society
• Peer Reviewed: Peer Reviewed
• Volume: 12
• Issue: 108
• DOI: https://doi.org/10.1098/rsif.2015.0391
• Keywords: Eye lens, Cell proliferation, Ageing, Cataract, Mathematical model, Scaling.
• Public URL: https://durham-repository.worktribe.com/output/1397954