Frederique M.D. Tholozan
Durham University
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Publication
Featured researches published by Frederique M.D. Tholozan.
Experimental Eye Research | 2014
Weiju Wu; Frederique M.D. Tholozan; Martin W. Goldberg; Leon Bowen; Jun Jie Wu; Roy A. Quinlan
Fibroblast growth factors play a key role in regulating lens epithelial cell proliferation and differentiation via an anteroposterior gradient that exists between the aqueous and vitreous humours. FGF-2 is the most important for lens epithelial cell proliferation and differentiation. It has been proposed that the presentation of FGF-2 to the lens epithelial cells involves the lens capsule as a source of matrix-bound FGF-2. Here we used immunogold labelling to measure the matrix-bound FGF-2 gradient on the inner surface of the lens capsule in flat-mounted preparations to visualize the FGF-2 available to lens epithelial cells. We also correlated FGF-2 levels with levels of its matrix-binding partner perlecan, a heparan sulphate proteoglycan (HSPG) and found the levels of both to be highest at the lens equator. These also coincided with increased levels of phosphorylated extracellular signal-regulated kinase 1 and 2 (pERK1/2) in lens epithelial cells that localised to condensed chromosomes of epithelial cells that were Ki-67 positive. The gradient of matrix-bound FGF-2 (anterior pole: 3.7 ± 1.3 particles/μm2; equator: 8.2 ± 1.9 particles/μm2; posterior pole: 4 ± 0.9 particles/μm2) and perlecan (anterior pole: 2.1 ± 0.4 particles/μm2; equator: 5 ± 2 particles/μm2; posterior pole: 1.9 ± 0.7 particles/μm2) available at the inner lens capsule surface was measured for the bovine lens. These data support the anteroposterior gradient hypothesis and provide the first measurement of the gradient for an important morphogen and its HSPG partner, perlecan, at the epithelial cell-lens capsule interface.
Journal of the Royal Society Interface | 2015
Jun Jie Wu; Weiju Wu; Frederique M.D. Tholozan; Christopher D. Saunter; John M. Girkin; Roy A. Quinlan
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.
Molecular Biology of the Cell | 2007
Frederique M.D. Tholozan; Christopher Gribbon; Zheng Li; Martin W. Goldberg; Alan R. Prescott; Norman McKie; Roy A. Quinlan
The International Journal of Biochemistry & Cell Biology | 2007
Frederique M.D. Tholozan; Roy A. Quinlan
Experimental Eye Research | 2008
Yuki Sugiyama; Alan R. Prescott; Frederique M.D. Tholozan; Shigeo Ohno; Roy A. Quinlan
Experimental Eye Research | 2007
Frederique M.D. Tholozan; John M. Sanderson; Roy A. Quinlan
Investigative Ophthalmology & Visual Science | 2003
Frederique M.D. Tholozan; Christopher Gribbon; Roy A. Quinlan; Alan R. Prescott
Archive | 2012
Roy A. Quinlan; Frederique M.D. Tholozan
Investigative Ophthalmology & Visual Science | 2011
Roy A. Quinlan; Frederique M.D. Tholozan; Weiju Wu
Investigative Ophthalmology & Visual Science | 2010
Roy A. Quinlan; Weiju Wu; C. D. Saunter; N. S. Holliman; Jun Jie Wu; Frederique M.D. Tholozan; G.F.J.M. Vrensen