May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Conditional Depletion of aPKC in Eye Lens Causes Microphthalmia and Cataract
Author Affiliations & Notes
  • Y. Sugiyama
    Experimental Ophthalmology, Save Sight Inst, University of Sydney, Sydney, Australia
    Molecular Biology, Yokohama City University Graduate School of Medical Science, Yokohama, Japan
  • K. Akimoto
    Molecular Biology, Yokohama City University Graduate School of Medical Science, Yokohama, Japan
  • M. L. Robinson
    Molecular & Human Genetics, Children's Research Institute, Ohio, Ohio
  • R. A. Quinlan
    School of Biological and Biomedical Sciences, Durham University, Durham, United Kingdom
  • S. Ohno
    Molecular Biology, Yokohama City University Graduate School of Medical Science, Yokohama, Japan
  • Footnotes
    Commercial Relationships  Y. Sugiyama, None; K. Akimoto, None; M.L. Robinson, None; R.A. Quinlan, None; S. Ohno, None.
  • Footnotes
    Support  Wellcome Trust, Naito Foundation Japan
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 2786. doi:https://doi.org/
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      Y. Sugiyama, K. Akimoto, M. L. Robinson, R. A. Quinlan, S. Ohno; Conditional Depletion of aPKC in Eye Lens Causes Microphthalmia and Cataract. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2786. doi: https://doi.org/.

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

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Abstract

Purpose: : The eye lens is mainly constituted of extremely elongate lens fibre cells, whose highly-organised anterior-posterior alignment ensures lens transparency, but the mechanism to orchestrate it has remained unclear. The lens fibre cells have apical-basal polarity with extended lateral membranes, and form apical cell junctions at the apical tips. The apical-basal polarity and the apical cell junctions are established in lens epithelial cells, the progenitors of the lens fibre cells, and maintained during differentiation to be transferred into lens fibre cells. Here, we focus on the role of the aPKC-Par system, an evolutionarily-conserved molecular machinery required for both of apical-basal polarity and apical cell junction formation in common epithelial cells, to understand the mechanism regulating highly-organised anterior-posterior alignment of lens fibre cells.

Methods: : A conditional knockout approach was used to selectively remove aPKC from the lens using the lens-specific transgenic expression of Cre. Lens morphology was monitored through development and up to postnatal week 8.

Results: : We found that conditional knockout of aPKC allele in lens by using MLR10 Cre transgenic mice caused microphthalmia (small lens) and cataract formation in postnatal life. Although overall constitution of the embryonic lenses of the conditional knockouts was maintained, the fibre cell alignment was seriously disrupted. We detected apical tips of differentiating fibre cells were detached from those of lens epithelial cells and failed to form the characteristic "turning point" at the lens equator. This defect leads disorganised fibre cell alignment that can be most likely cause of the cataract. We also found an unexpected role of aPKC in lens growth. Loss of aPKC decreased proliferative population of lens epithelial cells and induced ectopic fibre cell differentiation in the germinative zone. aPKC depletion also caused epithelial-mesenchymal transition of lens epithelial cells which may impair differentiation potency. These abnormalities deprive epithelial pool to differentiation and appears to be a main cause to abrogate lens growth.

Conclusions: : We conclude the equatorial turning point structure is essential for lens fibre cell alignment. We also indicate aPKC is required for maintenance of lens fibre cell progenitors.

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