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