May 2006
Volume 47, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2006
Deletion of the ß1–Integrin Gene in the Developing Lens Leads to Epithelial Mesenchymal Transition (EMT) of Lens Epithelial Cells
Author Affiliations & Notes
  • M.K. Duncan
    Biological Sciences, University of Delaware, Newark, DE
  • V.N. Simirskii
    Biological Sciences, University of Delaware, Newark, DE
  • Footnotes
    Commercial Relationships  M.K. Duncan, None; V.N. Simirskii, None.
  • Footnotes
    Support  NEI Grant RO1 EY015279–01
Investigative Ophthalmology & Visual Science May 2006, Vol.47, 2942. doi:
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      M.K. Duncan, V.N. Simirskii; Deletion of the ß1–Integrin Gene in the Developing Lens Leads to Epithelial Mesenchymal Transition (EMT) of Lens Epithelial Cells . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2942.

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

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Abstract

Purpose: : ß1–integrin is the major ß–integrin subunit expressed by the lens. Numerous studies have implicated ß1–integrins in both normal lens development and the pathogenesis of posterior capsular opacification, however, its function in vivo has not been addressed during lens development.

Methods: : Mice harboring a floxed ß1–integrin gene were mated with either MLR10–CRE or MLR39–CRE mice to inactive the ß1–integrin gene in either the entire lens or only the lens fiber cells respectively. The efficiency of the gene deletion was assayed by both PCR analysis of genomic DNA and confocal immunofluorescence analysis of ß1–integrin protein expression. The phenotype of the resulting animals was assayed by conventional histology and confocal immunofluoresence analysis of lens and EMT markers during development.

Results: : Mice homozygous for the floxed ß1–integrin gene harboring MLR10–CRE were microophthalmic, with little to no lens material detectable in adults. However, at 12.5 dpc, the lenses of these animals are morphologically normal with clearly distinguishable lens epithelial and fiber cells although no ß1–integrin protein is detected by confocal immunofluorescence.. The lens capsule also appears to form normally with type IV collagen and laminin detectable in this structure. However, at 16.5 dpc, lens epithelial cell shape becomes abnormal and and α–smooth muscle actin expression is detectable in these cells. At birth, the central lens epithelium is absent and the remaining epithelial cells at the periphery uniformly express α–smooth muscle actin. The remainder of the lens is highly vacuolated and the lens capsule has disappeared. Mice homozygous for the floxed ß1–integrin gene harboring MLR39–CRE lack exon 3 of the ß1–integrin gene specifically in lens fiber cells as assayed by genomic PCR. The eyes of adult mice harboring these genes are of normal size, although a significant proportion of their lenses develop cataracts.

Conclusions: : ß1–integrin is not necessary for either the early morphogenesis of the lens nor the development of the lens capsule. However, it is important to maintain the epithelial phenotype of lens epithelial cells later in development and its loss appears to result in inappropriate epithelial–mesenchymal transitions.

Keywords: cell adhesions/cell junctions • crystalline lens • EMT (epithelial mesenchymal transition) 
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