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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: 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 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 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.


Related in: MedlinePlus

Cell shape and cell organizational changes across the bovine lens epithelium. (a,b) Cell profiles in CZ, GZ, TZ and MR of the flat-mounted bovine lens epithelium. Using the apical plasma membrane marker ZO-1 (red channel), the cells in the CZ (a) have the largest surface area (see electronic supplementary material, figure S1a). At the MR (b), the lens cells aligned into columns. Cells in the MRs have a hexagonal profile. Each column in the MR is offset by half a cell width to allow the interdigitation of neighbouring columns. (c) Actin staining in the TZ/MR is located mainly on the lateral (arrowheads) and apical (arrows) cell membrane in these elongated cells. Cell nuclei have been DAPI stained (blue channel) locate toward the apical ends of the lens cells. (d) N-cadherin (green channel) is concentrated along the lateral plasma membranes of lens fibre cells (arrows). It is also concentrated at the interface between the apical ends of epithelial cells in the TZ/MR and the most recently formed fibre cell (arrowheads). The concentration of N-cadherin between the two arrows at the interface between the apical ends of apposed epithelial and fibre cells identifies a region, which we interpret as the lens modiolus and fulcrum.
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RSIF20150391F4: Cell shape and cell organizational changes across the bovine lens epithelium. (a,b) Cell profiles in CZ, GZ, TZ and MR of the flat-mounted bovine lens epithelium. Using the apical plasma membrane marker ZO-1 (red channel), the cells in the CZ (a) have the largest surface area (see electronic supplementary material, figure S1a). At the MR (b), the lens cells aligned into columns. Cells in the MRs have a hexagonal profile. Each column in the MR is offset by half a cell width to allow the interdigitation of neighbouring columns. (c) Actin staining in the TZ/MR is located mainly on the lateral (arrowheads) and apical (arrows) cell membrane in these elongated cells. Cell nuclei have been DAPI stained (blue channel) locate toward the apical ends of the lens cells. (d) N-cadherin (green channel) is concentrated along the lateral plasma membranes of lens fibre cells (arrows). It is also concentrated at the interface between the apical ends of epithelial cells in the TZ/MR and the most recently formed fibre cell (arrowheads). The concentration of N-cadherin between the two arrows at the interface between the apical ends of apposed epithelial and fibre cells identifies a region, which we interpret as the lens modiolus and fulcrum.

Mentions: In §4.4, we considered how to model the decrease in the cell-density profile from the peak to the reduced density in the MR and the immediately adjacent TZ at the lens periphery. The reduction in cell density is greater than the minor change that would be predicted from a consideration of the increasing value of the circumference with radius. There is an active reduction in cell density and we present experimental data showing how cell–cell interactions are different within this region of the lens epithelium. For example, we highlight the formation of N-cadherin homotypic junctions between the apical ends of the epithelial cells and their apposed lens fibre cells (figure 4).Figure 4.


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)

Cell shape and cell organizational changes across the bovine lens epithelium. (a,b) Cell profiles in CZ, GZ, TZ and MR of the flat-mounted bovine lens epithelium. Using the apical plasma membrane marker ZO-1 (red channel), the cells in the CZ (a) have the largest surface area (see electronic supplementary material, figure S1a). At the MR (b), the lens cells aligned into columns. Cells in the MRs have a hexagonal profile. Each column in the MR is offset by half a cell width to allow the interdigitation of neighbouring columns. (c) Actin staining in the TZ/MR is located mainly on the lateral (arrowheads) and apical (arrows) cell membrane in these elongated cells. Cell nuclei have been DAPI stained (blue channel) locate toward the apical ends of the lens cells. (d) N-cadherin (green channel) is concentrated along the lateral plasma membranes of lens fibre cells (arrows). It is also concentrated at the interface between the apical ends of epithelial cells in the TZ/MR and the most recently formed fibre cell (arrowheads). The concentration of N-cadherin between the two arrows at the interface between the apical ends of apposed epithelial and fibre cells identifies a region, which we interpret as the lens modiolus and fulcrum.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

RSIF20150391F4: Cell shape and cell organizational changes across the bovine lens epithelium. (a,b) Cell profiles in CZ, GZ, TZ and MR of the flat-mounted bovine lens epithelium. Using the apical plasma membrane marker ZO-1 (red channel), the cells in the CZ (a) have the largest surface area (see electronic supplementary material, figure S1a). At the MR (b), the lens cells aligned into columns. Cells in the MRs have a hexagonal profile. Each column in the MR is offset by half a cell width to allow the interdigitation of neighbouring columns. (c) Actin staining in the TZ/MR is located mainly on the lateral (arrowheads) and apical (arrows) cell membrane in these elongated cells. Cell nuclei have been DAPI stained (blue channel) locate toward the apical ends of the lens cells. (d) N-cadherin (green channel) is concentrated along the lateral plasma membranes of lens fibre cells (arrows). It is also concentrated at the interface between the apical ends of epithelial cells in the TZ/MR and the most recently formed fibre cell (arrowheads). The concentration of N-cadherin between the two arrows at the interface between the apical ends of apposed epithelial and fibre cells identifies a region, which we interpret as the lens modiolus and fulcrum.
Mentions: In §4.4, we considered how to model the decrease in the cell-density profile from the peak to the reduced density in the MR and the immediately adjacent TZ at the lens periphery. The reduction in cell density is greater than the minor change that would be predicted from a consideration of the increasing value of the circumference with radius. There is an active reduction in cell density and we present experimental data showing how cell–cell interactions are different within this region of the lens epithelium. For example, we highlight the formation of N-cadherin homotypic junctions between the apical ends of the epithelial cells and their apposed lens fibre cells (figure 4).Figure 4.

Bottom Line: 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 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 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.


Related in: MedlinePlus