ArticleHuman molecular genetics2017
Transgenic TBK1 mice have features of normal tension glaucoma.
Article in Human molecular genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.
- Genome-wide meta-analysis identifies 22 loci for normal tension glaucoma with significant overlap with high tension glaucoma.Nature communications · 2024Pooled it
- TBK1 overexpression reduces neuronal loss in the P497S UBQLN2 mouse model of ALS/FTD.Neurobiology of disease · 2026Article
- Autophagy in ocular diseases: from mechanisms to therapeutic potential.Frontiers in cell and developmental biology · 2026Review
- Experimental models to study oxidative stress in glaucoma: integratingFrontiers in pharmacology · 2026Review
- Emerging strategies targeting genes and cells in glaucoma.Vision research · 2025Review
- Tank-binding kinase 1 regulates inflammation and autophagy in glaucoma.Frontiers in neuroscience · 2025Review
- Molecular pathways in experimental glaucoma models.Frontiers in neuroscience · 2024Review
- Glaucoma: from pathogenic mechanisms to retinal glial cell response to damage.Frontiers in cellular neuroscience · 2024Review
- Review
- TBK1 Knockdown Alleviates Axonal Transport Deficits in Retinal Ganglion Cells Via mTORC1 Activation in a Retinal Damage Mouse Model.Investigative ophthalmology & visual science · 2023Article
- The RNA-binding protein and stress granule component ATAXIN-2 is expressed in mouse and human tissues associated with glaucoma pathogenesis.The Journal of comparative neurology · 2022Article
- Diffusion Tensor Imaging of Visual Pathway Abnormalities in Five Glaucoma Animal Models.Investigative ophthalmology & visual science · 2021Article
- Review
- Neuroinflammatory Mechanisms of Mitochondrial Dysfunction and Neurodegeneration in Glaucoma.Journal of ophthalmology · 2021Review
- Immunogenetics of the Ocular Anterior Segment: Lessons from Inherited Disorders.Journal of ophthalmology · 2021Review
- Role of animal models in glaucoma research.Neural regeneration research · 2020Article
- The Genetic and Endoplasmic Reticulum-Mediated Molecular Mechanisms of Primary Open-Angle Glaucoma.International journal of molecular sciences · 2020Review
- Long-Term Follow-Up of Normal Tension Glaucoma Patients With TBK1 Gene Mutations in One Large Pedigree.American journal of ophthalmology · 2020Article
- Inducible rodent models of glaucoma.Progress in retinal and eye research · 2020Review
- Differential DNA methylation patterns in human Schlemm's canal endothelial cells with glaucoma.Molecular vision · 2020Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Duplication of the TBK1 gene is associated with 1-2% of normal tension glaucoma, a common cause of vision loss and blindness that occurs without grossly abnormal intraocular pressure. We generated a transgenic mouse that has one copy of the human TBK1 gene (native promoter and gene structure) incorporated into the mouse genome (Tg-TBK1). Expression of the TBK1 transgene in the retinae of these mice was demonstrated by real-time PCR. Using immunohistochemistry TBK1 protein was predominantly localized to the ganglion cell layer of the retina, the cell type most affected by glaucoma. More intense TBK1 labelling was detected in the retinal ganglion cells (RGCs) of Tg-TBK1 mice than in wild-type littermates. Tg-TBK1 mice exhibit the cardinal sign of glaucoma, a progressive loss of RGCs. Hemizygous Tg-TBK1 mice (with one TBK1 transgene per genome) had a 13% loss of RGCs by 18 months of age (P = 1.5 × 10-8). Homozygous Tg-TBK1 mice had 7.6% fewer RGCs than hemizygous Tg-TBK1 mice and 20% fewer RGCs than wild-type mice (P = 1.9 × 10-5) at 6 months of age. No difference in intraocular pressures was detected between Tg-TBK1 mice and wild-type littermates as they aged (P > 0.05). Tg-TBK1 mice with extra doses of the TBK1 gene recapitulate the phenotype of normal tension glaucoma in human patients with a TBK1 gene duplication. Together, these studies confirm the pathogenicity of the TBK1 gene duplication in human glaucoma and suggest that excess production of TBK1 kinase may have a role in the pathology of glaucoma.
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Registered trials
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