June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Abnormal Development and Differentiation of the Periocular Mesenchyme in AP-2β Neural Crest Cell Knockout Mice
Author Affiliations & Notes
  • Monica Akula
    Pathology and Molecular Medicine, McMaster University, Toronto, Ontario, Canada
  • Vanessa Martino
    Pathology and Molecular Medicine, McMaster University, Toronto, Ontario, Canada
  • Trevor Williams
    Molecular Biology, University of Colorado, Denver, Colorado, United States
  • Judith A West-Mays
    Pathology and Molecular Medicine, McMaster University, Toronto, Ontario, Canada
  • Footnotes
    Commercial Relationships   Monica Akula, None; Vanessa Martino, None; Trevor Williams, None; Judith West-Mays, None
  • Footnotes
    Support  NIH EY025789
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 1730. doi:
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    • Get Citation

      Monica Akula, Vanessa Martino, Trevor Williams, Judith A West-Mays; Abnormal Development and Differentiation of the Periocular Mesenchyme in AP-2β Neural Crest Cell Knockout Mice. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1730.

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

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Abstract

Purpose : Previously, our lab showed that deletion of AP-2β transcription factor in neural crest cells contributing to the periocular mesenchyme (POM) (AP-2β NCC KO) resulted in anterior segment defects, including absence of a corneal endothelium, iridocorneal adhesions and outflow pathway defects accompanied by raised intraocular pressure (IOP). To better understand the cause of these defects this study purports to examine the embryonic patterns and differentiation of the POM in AP-2β NCC KO mice.

Methods : Wnt1Cre+/-/Tcfap2b+/- mice were bred with Tcfap2blox/lox mice to generate Wnt1Cre+/-/Tcfap2b-/lox mice (AP-2β NCC KO) with Tcfap2b, encoding AP-2β, deleted in the neural crest. Immunohistochemistry of paraffin embedded AP-2β NCC KO and control littermate eyes was done at embryonic day (E) 10.5, E15.5 and in postnatal mice using antibodies against phospho-histone H3, Pitx2, α-smooth muscle actin (α-SMA) and myocilin, an extracellular matrix component.

Results : At E10.5 the POM was more loosely arranged in AP-2β NCC KO mice compared with control littermates (n=3). At E15.5 proliferation (n=2) and Pitx2 localization (n=2) were reduced in the corneal endothelium of mutant mice, and the 2nd wave of newly migrated Pitx2 positive POM cells appeared adhered to the cornea in AP-2β NCC KO mice, which was not observed in controls (n=2). Furthermore, myocilin (n=1) and α-SMA (n=3) expression were substantially reduced in the trabecular meshwork of postnatal mutant mice as compared to controls.

Conclusions : The loose arrangement of the POM at E10.5, and reduced corneal endothelium proliferation and Pitx2 localization at E15.5 in the mutant mice suggests that POM cells are not differentiating appropriately into corneal specific cell types. The fact that at E15.5 the 2nd wave of POM cells in the mutants were adhered to the corneal endothelium suggests that this may be contributing to the iridocorneal adhesions observed at postnatal stages. Additionally, reduced expression of α-SMA and myocilin suggests that POM cells in the mutants are not differentiating into the appropriate cell types when compared to control littermates. Together, the observed defects in both POM placement and differentiation likely underlie the anterior segment defects that contribute to the increased IOP observed in the mutant mice.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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