Abstract

Organ and tissue development are highly coordinated processes; lens growth and functional integration into the eye (emmetropia) is a robust example. An epithelial monolayer covers the anterior hemisphere of the lens, and its organization is the key to lens formation and its optical properties throughout all life stages. To better understand how the epithelium supports lens function, we have developed a novel whole tissue imaging system using conventional confocal light microscopy and a specialized analysis software to produce three-dimensional maps for the epithelium of intact mouse lenses. The open source software package geometrically determines the anterior pole position, the equatorial diameter, and three-dimensional coordinates for each detected cell in the epithelium. The user-friendly cell maps, which retain global lens geometry, allow us to document age-dependent changes in the C57/BL6J mouse lens cell distribution characteristics. We evidence changes in epithelial cell density and distribution in C57/BL6J mice during the establishment of emmetropia between postnatal weeks 4–6. These epithelial changes accompany a previously unknown spheroid to lentoid shape transition of the lens as detected by our analyses. When combined with key findings from previous mouse genetic and cell biological studies, we suggest a cytoskeleton-based mechanism likely underpins these observations.

Highlights

  • Organ and tissue development are highly coordinated processes; lens growth and functional integration into the eye is a robust example

  • Lens epithelial cells (LECs) form a cuboidal monolayer on the anterior half of the tissue, which differentiate into lens fiber cells (LFCs) at the lens equator, where they internalize and continually add to the lens mass throughout ­life[14]

  • The separation of the high density LEC zone from the central zone (CZ) at maturation is concurrent with the transition from spheroid to lentoid shape between 4 and 6 weeks

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Summary

Introduction

Organ and tissue development are highly coordinated processes; lens growth and functional integration into the eye (emmetropia) is a robust example. The postnatal period of development is where the most accelerated growth phase takes place and when the growth of the different tissues of the eye is integrated to deliver the required visual p­ roperties[5]. These vary between mammals and are related to their environment and behaviors, for example whether they are nocturnal or a­ quatic[4,6]. As LECs are the reservoir of all future fiber cells, it is important to know how LEC organization changes during lens ageing and at key stages of growth, especially those that potentially determine the functional contribution of the lens to v­ ision[7]. Mathematical models of the lens epithelium have been p­ roduced[11,18], but they have used methodologies that could introduce inaccuracies into the measurements, of the small, round lenses of mice, rats and zebrafish

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