June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
What is the role of the pre-germinative zone?
Author Affiliations & Notes
  • Hrvoje Sikic
    Ophthalmology and Visual Sciences, Washington University, St. Louis, MO
    Mathematics, University of Zagreb, Faculty of Science, Zagreb, Croatia
  • Snjezana Lubura
    Mathematics, University of Zagreb, Faculty of Science, Zagreb, Croatia
  • Steven Bassnett
    Ophthalmology and Visual Sciences, Washington University, St. Louis, MO
  • Footnotes
    Commercial Relationships Hrvoje Sikic, None; Snjezana Lubura, None; Steven Bassnett, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 2624. doi:
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      Hrvoje Sikic, Snjezana Lubura, Steven Bassnett; What is the role of the pre-germinative zone?. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2624.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: In the adult mouse lens epithelium the proliferation index varies with latitude. Near the lens equator, a 300 μm-wide germinative zone (GZ) shows the highest rate of cell proliferation. Anterior to the GZ is a 400 μm-wide swath of cells called the pre-germinative zone (PGZ). The rate of cell division in the PGZ is approximately 10-fold lower than in the GZ. In this study, we used a stochastic model to explore the specific contribution of the PGZ to lens growth.

Methods: Cell division within the epithelium was modeled as a branching process with emigration and immigration between the various proliferative zones. Empirically measured changes in cell area were included in the model as a deterministic function.

Results: Model analysis suggested that the PGZ may serve several roles in the epithelial layer. First, it supplies cells to the otherwise proliferatively quiescent central zone (CZ) of the epithelium. The PGZ also supplies cells to the main growth engine of the lens, the GZ, allowing it to maintain its proper size. The PGZ functions as a buffer region between the inert CZ and the stochastically active GZ, helping ensure smooth and precise lens growth in the face of stochastic fluctuations in cell division rate. As a consequence of these features, the PGZ contains a cellular watershed. Cells located north of this virtual line are likely to be incorporated into the expanding CZ. Cells south of the watershed are likely to eventually differentiate and enter the fiber cell compartment.

Conclusions: Mathematical modeling suggests that the PGZ may have an important role in regulating the ultimate disposition of epithelial cells located considerable distances from the lens equator. The cellular watershed may serve to restrict the movement of epithelial cells initially located in the pupil space. If such cells are prone to UV-induced somatic mutations, these would be effectively blocked from entering the fiber cell compartment.

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