June 2013
Volume 54, Issue 15
ARVO Annual Meeting Abstract  |   June 2013
Transgenic TBK1 mouse develops signs of normal tension glaucoma
Author Affiliations & Notes
  • John Fingert
    Ophthalmology, University of Iowa, Iowa City, IA
  • Kathy Miller
    Ophthalmology, University of Iowa, Iowa City, IA
  • Frances Solivan-Timpe
    Ophthalmology, University of Iowa, Iowa City, IA
  • Ben Roos
    Ophthalmology, University of Iowa, Iowa City, IA
  • Alan Robin
    Ophthalmology and International Health, Johns Hopkins University, Baltimore, MD
  • Robert Mullins
    Ophthalmology, University of Iowa, Iowa City, IA
  • Michael Anderson
    Physiology, University of Iowa, Iowa City, IA
  • Footnotes
    Commercial Relationships John Fingert, None; Kathy Miller, None; Frances Solivan-Timpe, None; Ben Roos, None; Alan Robin, merck (C), merck (R), Aerie (C), Aerie (I), Sucampo (E), Glaukos (C), Glaukos (I), Allergan (R); Robert Mullins, Alcon Research Ltd (F); Michael Anderson, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 4971. doi:
  • Views
  • Share
  • Tools
    • Alerts
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      John Fingert, Kathy Miller, Frances Solivan-Timpe, Ben Roos, Alan Robin, Robert Mullins, Michael Anderson; Transgenic TBK1 mouse develops signs of normal tension glaucoma. Invest. Ophthalmol. Vis. Sci. 2013;54(15):4971.

      Download citation file:

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

  • Supplements

Purpose: To generate a transgenic mouse with the same TANK-binding kinase 1 (TBK1) mutations that cause normal tension glaucoma (NTG) in humans and to characterize the features of glaucoma in these transgenic mice.

Methods: Transgenic TBK1 mice were generated using a BAC vector to integrate the human TBK1 gene (with native promoter and intron sequences) into the mouse genome. Aged transgenic mice and littermates were evaluated for features of glaucoma with tonometry, optical coherence tomography (OCT), retinal ganglion cell counts, and optic nerve axon counts.

Results: Baseline examinations, showed no elevation of IOP, and no retinal abnormalities on clinical, OCT, or histological examiations. At 7 months, transgenic mice (n=13) and wild-type littermates (n=13) showed no elevation in intraocular pressure. Retinal ganglion cell counts were reduced in the transgenic mice by 9.6% when compared with littermates (p < 0.001). Preliminary counts of optic nerve axon counts are also reduced but are still underway.

Conclusions: Copy number variations (gene duplication) in TBK1 have been associated by NTG. Here we report the first data showing that a similar gene defect engineered in transgenic mice also produces an NTG phenotype. Preliminary studies of transgenic TBK1 mice show that they develop features of glaucoma (reduced retinal ganglion cell counts) in the absence of elevated intraocular pressure. These data suggest that this model system will be a useful resource for investigating the causes of optic nerve damage in glaucoma. Futhermore, these mice may also be used to test new diagnostic and therapeutic approaches for human glaucoma. Larger cohorts of mice are being aged further and will provide even more definitive data to support these conclusions.

Keywords: 539 genetics • 740 transgenics/knock-outs • 629 optic nerve  

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.