April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
Cytoskeletal Regulation of Collective Migration During PCO
Author Affiliations & Notes
  • Janice L. Walker
    Pathology/Anatomy&Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania
  • Brigid M. Bleaken
    Pathology/Anatomy&Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania
  • Ni Zhai
    Pathology/Anatomy&Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania
  • Liping Zhang
    Pathology/Anatomy&Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania
  • A. Sue Menko
    Pathology/Anatomy&Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania
    Wills Eye Institute, Philadelphia, Pennsylvania
  • Footnotes
    Commercial Relationships  Janice L. Walker, None; Brigid M. Bleaken, None; Ni Zhai, None; Liping Zhang, None; A. Sue Menko, None
  • Footnotes
    Support  EY010577, EY14258, EY014798 and EY019571
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 4777. doi:
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      Janice L. Walker, Brigid M. Bleaken, Ni Zhai, Liping Zhang, A. Sue Menko; Cytoskeletal Regulation of Collective Migration During PCO. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4777.

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

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Abstract

Purpose: : Posterior Capsular Opacification (PCO) is a lens fibrotic disease that results in part from the collective migration of residual cells onto the posterior capsule. Using an ex vivo chick lens capsular bag model for PCO which allows us to study the movement of lens epithelial cells onto the endogenous posterior capsule, we examined the cytoskeletal and signaling mechanisms that regulate the collective migration of cells during this disease process.

Methods: : Following mock cataract surgery in chick embryo lenses, collective migration was examined in this ex vivo PCO culture models in the presence and absence of inhibitors of cytoskeletal function.

Results: : Our studies revealed distinct cytoskeletal organization in the population of leader cells at the wound edge and follower lens epithelial cells as they collectively migrate onto the posterior capsule. Leader cells, rich in vimentin, extended microtubules to their protruding edges, and formed paxillin focal adhesions with a unique linkage to the vimentin cytoskeleton. Studies in follower cells revealed a concentration of α-tubulin at apical cell-cell borders and, surprisingly, the extension of primary cilia from each of these cells, which are likely critical to sensing the direction of movement within this migrating sheet. Disruption of microtubules led to the concomitant disorganization of vimentin and decreased migration. One way that follower cells appear to contribute to movement across the capsule is through their formation of cryptic lamellipodia along the basal aspects of the cells enriched with N-cadherin, cortactin and actin. This was supported by our finding that inhibiting Rac activity, critical to the role of the actin cytoskeleton in lamellipodial function, was necessary for sheet movement across the posterior capsule. Myosin IIB, a factor believed to be critical to movement and force generation, localized uniquely to the vertices of the linear cell-cell contacts between the migrating lens epithelial cells. Drug induced loss of myosin function led to disorganization of the migrating monolayer and decreased cell-cell interactions and increased cell migration. These results suggest myosin function is critical for maintaining cell-cell contacts of follower cells and for regulating migration across the posterior capsule.

Conclusions: : The migration of lens epithelial cells in PCO is regulated by a complex coordination of cytoskeletal signals.

Keywords: posterior capsular opacification (PCO) • cytoskeleton • cell-cell communication 
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