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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 JJ, Wu W, Tholozan FM, Saunter CD, Girkin JM, Quinlan RA - J R Soc Interface (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

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.

No MeSH data available.


Variation of measured cell density with age in the lens epithelium of mammals. (a) Line plots for mouse lenses of different ages. (b) Line plots for human lenses of different ages.
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RSIF20150391F3: Variation of measured cell density with age in the lens epithelium of mammals. (a) Line plots for mouse lenses of different ages. (b) Line plots for human lenses of different ages.

Mentions: To emphasize the evolution of cell density with age, the data for mouse and human lenses are shown as line plots (figure 3a,b). The measured cell densities were plotted against actual distance from the anterior pole in order to track the change in both lens size and epithelial cell density. Comparing the data for mouse lenses of different ages (figure 3a), there is an abrupt peak for young mice as found in other young mammals (figure 2b). This peak broadens with increasing mouse age (figure 3a). A distinct peak in cell density similar to that seen in the animal lens data is absent from our human data (figure 3b). In the four age groups of adult (more than 20 years) human lenses, the cell-density maxima in the periphery (1.38 mm in length) consistently declined with age (figure 3b). Significant differences between lens cell density profiles for the age groups 20–30 versus 40–50, 20–30 versus 60–70, 20–30 versus 80–90, and 40–50 versus 80–90 were observed (p < 0.05); the highest cell density of the oldest group had dropped by approximately 25% compared with the youngest group's. We note that the cell density maxima of the youngest human lenses were close to that of the bovine lenses (less than 30 months).Figure 3.


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 JJ, Wu W, Tholozan FM, Saunter CD, Girkin JM, Quinlan RA - J R Soc Interface (2015)

Variation of measured cell density with age in the lens epithelium of mammals. (a) Line plots for mouse lenses of different ages. (b) Line plots for human lenses of different ages.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4528606&req=5

RSIF20150391F3: Variation of measured cell density with age in the lens epithelium of mammals. (a) Line plots for mouse lenses of different ages. (b) Line plots for human lenses of different ages.
Mentions: To emphasize the evolution of cell density with age, the data for mouse and human lenses are shown as line plots (figure 3a,b). The measured cell densities were plotted against actual distance from the anterior pole in order to track the change in both lens size and epithelial cell density. Comparing the data for mouse lenses of different ages (figure 3a), there is an abrupt peak for young mice as found in other young mammals (figure 2b). This peak broadens with increasing mouse age (figure 3a). A distinct peak in cell density similar to that seen in the animal lens data is absent from our human data (figure 3b). In the four age groups of adult (more than 20 years) human lenses, the cell-density maxima in the periphery (1.38 mm in length) consistently declined with age (figure 3b). Significant differences between lens cell density profiles for the age groups 20–30 versus 40–50, 20–30 versus 60–70, 20–30 versus 80–90, and 40–50 versus 80–90 were observed (p < 0.05); the highest cell density of the oldest group had dropped by approximately 25% compared with the youngest group's. We note that the cell density maxima of the youngest human lenses were close to that of the bovine lenses (less than 30 months).Figure 3.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

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.

No MeSH data available.