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.
Highlights
Vision is one of the most important senses for survival and the eye and the eye lens have evolved in ways that are linked closely with an animal’s environment
We developed the first mathematical model of cell-density distribution in the lens epithelium of animal lenses
We showed that there are species-independent profiles for adolescent mammals, if the data are normalized based upon the size of central zone (CZ)
Summary
Vision is one of the most important senses for survival and the eye and the eye lens have evolved in ways that are linked closely with an animal’s environment. The lens integrates cell structure with tissue form to produce a graded refractive index that reduces spherical aberration to enhance vision in animals [1]. The lens grows throughout life [2] and is a tissue in which both biological and physical forces combine in its formation. A monolayer of polarized epithelial cells grows on the inner anterior surface of the lens capsule [3], with their apical ends facing the lens interior and contacting the apical ends of the underlying fibre cells that are part of the lens cortex, an interaction that regulates epithelial cell proliferation [4,5]. The eye is growing one can envisage at any particular age a population balance at every radial position where the net production of cells is balanced by their migration towards the periphery. The bulk of the lens comprises fibre cells
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