title: 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.
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 γ(GZ), 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.
authors.forename: Jun Jie
authors.initials: JJ
authors.lastname: Wu
authors.forename: Weiju
authors.initials: W
authors.lastname: Wu
authors.forename: Frederique M
authors.initials: FM
authors.lastname: Tholozan
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Saunter
authors.forename: John M
authors.initials: JM
authors.lastname: Girkin
authors.forename: Roy A
authors.initials: RA
authors.lastname: Quinlan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D002417:Cattle; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007908:Lens, Crystalline / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008875:Middle Aged; D008954:Models, Biological; D011817:Rabbits; D051381:Rats; D013045:Species Specificity