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Hrvoje Sikic, Steven Bassnett; On cluster sizes during lens growth in the mouse. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3064.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Lineage tracing studies indicate that clonal cell clusters emerge in the mouse lens epithelium during development. Here, we use a stochastic growth model to explore the origin and possible significance of epithelial cell clusters. We focus on the period between three and six months of development, during which time a pause in the growth of cells in the central zone (CZ) of the epithelium temporarily blocks the flow of cells toward the germinative zone (GZ).
Methods: Biological growth parameters (distribution of proliferative cells, cell sizes, rates of radial growth, cell population, kinetics, etc.) were measured in lenses P90 to P180. Data were interpreted using a growth model (J. Theor Biol. 376:15). Based on the model, probabilistic calculations were performed to estimate cluster sizes.
Results: Due to a reduction in the proportion of S-phase cells in the GZ at six months compared to three months, calculations suggested that clusters of smaller average size will form. We provide likelihood estimates for clusters of various sizes for the three months and six-months-old lens. The pause in the expansion of CZ cells was shown to have a significant effect on the expected cluster size.
Conclusions: Use of a stochastic lens growth model allows the size of epithelial cell clusters to be calculated as a function of both time and latitudinal position on the lens surface. The distribution of predicted cluster sizes was consistent with results of lineage tracing studies. The pause in CZ growth from three to six months has the effect of skewing the cluster size distribution towards smaller values. We hypothesize that this effect would serve to minimize the likelihood of deleterious somatic mutations flowing from sun-exposed regions of the epithelium into the fiber cell body.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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