Publication details for Professor Jun Jie WuQuinlan, R.A., Wu, J.J., Wu, W., Saunter, C. & Girkin, J. (2015), A mathematical model of the eye lens epithelium of mammals that predicts cell density profiles in the ageing lens, ARVO 2015 Annual Meeting. Denver, Colorado, ARVO.
- Publication type: Conference Paper
- Further publication details on publisher web site
Author(s) from Durham
Purpose: To develop a mathematical model of the mammalian eye
lens epithelium that is independent of the lens size and that accounts
for the change in cell density from the anterior pole to the meridional
rows at the lens equator. The model aims to predict the age dependent
changes in cell density.
Methods: Eye lenses were dissected, the epithelial flat mounted
and then fixed and processed for immunofluoresence microscopy.
Fluoresence signal were detected using either a Zeiss LSM 510
Meta or Leica SP5 scanning confocal microscope. Cell density
measurements were made using DAPI and then bespoke software to
segment images. Lenses from mice up to 2 years and from human
donors from 20-90 years old were obtained with the required ethical,
animal and human tissue authorisations.
Results: The cellular distribution in the lens epithelium was
measured in mouse, rat, rabbit, bovine and human lenses from the
anterior pole of the lens to the meridional rows loacted at te lens
equator. Measurements of cell proliferation (Ki67) and cell death
(TUNEL) were also made. The epithelium was then modelled as a disk and an appropriate differential equation for the cell density
distribution was solved. At any given time-point, this differential
equation balances the pull-through due to fibre cell formation with
net epithelial cell proliferation. Cell proliferation is concentrated
in the peripheral region of the lens where the germinative zone is
located, with only baseline proliferation rates observed in the central
zone of the lens epithelium. The ratio of the per capita division
rate for these two zones as predicted from the model was found to
be equal to a recently measured gradient of matrix-bound FGF-
2 in the lens capsule. The model predicts that as the ratio of the
proliferation parameter to the pull-through parameter declines, so
the discrete peak in cell density found in the germinative zone will
decay. Measurements of ageing mouse and human lens epithelial cell
densities were used to affirm the predictive value of the model.
Conclusions: We have developed a model of the mammalian lens
epithelium that balances pull-through due to fibre cell formation with
net cell proliferation. The model predicts the morphogen gradient that
drives cell survival, cell proliferation and cell differentiation. It also
successfully predicts the cell density changes that accompany ageing
in the mouse lens.
Commercial Relationships: Roy A. Quinlan, None; Junjie Wu,
None; Weiju Wu, None; Chris Saunter, None; John Girkin, None
Support: Fight for Sight (#1358) and Leverhulme Trust (RPG-2012-