March 2012
Volume 53, Issue 14
Free
ARVO Annual Meeting Abstract  |   March 2012
Impaired Vision in the DNA Double-Strand Break Repair Polµ-mutant Mouse
Author Affiliations & Notes
  • Noemi L. Alvarez-Lindo
    Cellular and molecular medicine, Centro de Investigaciones Biologicas-CSIC, Madrid, Spain
  • Jimena Baleriola
    Cellular and molecular medicine, Centro de Investigaciones Biologicas-CSIC, Madrid, Spain
  • Jose Luis M. Sanmartin
    Cellular and molecular medicine, Centro de Investigaciones Biologicas-CSIC, Madrid, Spain
  • Teresa Suarez
    Cellular and molecular medicine, Centro de Investigaciones Biologicas-CSIC, Madrid, Spain
  • Gloria Terrados
    Centro de Biologia Molecular CSIC-UAM, Madrid, Spain
  • Beatriz Escudero
    Centro de Nacional de Investigaciones Cardiovasculares, Madrid, Spain
  • Antonio Bernad
    Centro de Nacional de Investigaciones Cardiovasculares, Madrid, Spain
  • Luis Blanco
    Centro de Biologia Molecular CSIC-UAM, Madrid, Spain
  • Pedro de la Villa
    Physiology, University of Alcala, Alcala de Henares, Spain
  • Enrique de la Rosa
    Cellular and molecular medicine, Centro de Investigaciones Biologicas-CSIC, Madrid, Spain
  • Footnotes
    Commercial Relationships  Noemi L. Alvarez-Lindo, None; Jimena Baleriola, None; Jose Luis M. Sanmartin, None; Teresa Suarez, None; Gloria Terrados, None; Beatriz Escudero, None; Antonio Bernad, None; Luis Blanco, None; Pedro de la Villa, None; Enrique de la Rosa, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 6493. doi:
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      Noemi L. Alvarez-Lindo, Jimena Baleriola, Jose Luis M. Sanmartin, Teresa Suarez, Gloria Terrados, Beatriz Escudero, Antonio Bernad, Luis Blanco, Pedro de la Villa, Enrique de la Rosa; Impaired Vision in the DNA Double-Strand Break Repair Polµ-mutant Mouse. Invest. Ophthalmol. Vis. Sci. 2012;53(14):6493.

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

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Abstract

Purpose: : During neural development, the distinctive cytoarchitecture and connectivity of the nervous system are achieved by an orchestrated balance of proliferation, differentiation and cell death. The physiological basis of an early phase of programmed cell death affecting recently born neurons is not understood. Several genetically-modified mouse model systems defective in DNA double-strand break (DSB) repair present a dramatic phenotype during neural development, suggesting a possible function of DNA repair in the process. Hereby, we try to demonstrate in vivo the requirement of Polµ, a DNA polymerase involved in DSB repair, for proper retinal development and function.

Methods: : We have analyzed retinal development and visual function in the Polµ deficient mouse, a murine model defective in DNA repair, as well as in its wild type counterpart. Whole mount and dissociated retinas were processed for immunohistochemistry and western blot to determine the effect of the mutation on neuronal differentiation, cell-adhesion molecule distribution, axonogenesis and cell death. Optic nerve architecture was visualiced by electron microscopy. Visual function in adult animals was analyzed by electroretinogram recording and optomotor test.

Results: : Polµ-/- mutant mice presented increased apoptotic cell death that selectively affected recently born retinal ganglion cells. Moreover, the intraretinal pattern of axonal growth, as well as optic nerve fasciculation and decussation at the optic quiasma were altered. These abnormalities may correlate with observed alterations in axonal-guidance proteins. Interestingly, the mutant mice present also a distortion in the motion perception.

Conclusions: : Proper DNA double-strand break repair during retinal neurogenesis is required to achieve accurate retinal function.

Keywords: retinal development • retinal degenerations: cell biology • visual impairment: neuro-ophthalmological disease 
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