DBA/2J mouse model for experimental glaucoma: pitfalls and problems

Anita J. Turner*, Roshana Vander Wall, Vivek Gupta, Alex Klistorner, Stuart L. Graham

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

Abstract

Background: The DBA/2J mouse has been described as a model for congenital experimental glaucoma. It develops anterior segment anomalies with synechiae and pigment dispersion leading to raised intraocular pressure and glaucomatous damage. However, there are serious practical considerations when using this model in longitudinal studies. Methods: We followed 118 mice from 12-48 weeks of age in a pharmaceutical trial. Here we report on the findings in control animals (n = 37). Intraocular pressure was measured weekly, electrophysiology and optical coherence tomography every 6 weeks. A subset also had invasive intraocular pressure measurements performed prior to euthanasia. Results: Although intraocular pressure eventually rose by 9 months in most animals, tonometry was complicated by corneal calcification in the majority of animals rendering intraocular pressure measurement unreliable. Invasive intraocular pressure did not correlate with non-invasive measures. Loss of scotopic threshold response and thinning of inner retinal layers on optical coherence tomography was observed over time, suggesting glaucomatous damage, but this occurred in some animals without raised intraocular pressure. Poor pupil dilation significantly affected electrophysiology, optical coherence tomography and fundus imaging; 22% of animals developed major systemic complications leading to high dropout rate. Conclusions: The DBA/2J experimental glaucoma model shows variability in expression, and its pathological changes cause major difficulties in assessing disease progression. From our experience, the model presents significant challenges for drug studies in glaucoma, as there are many confounding factors: difficulty with accurate intraocular pressure measurement, in vivo imaging, and electrophysiology recording and a high dropout rate. In addition, there may be an underlying neurodegenerative process independent of intraocular pressure.

Original languageEnglish
Pages (from-to)911-922
Number of pages12
JournalClinical and Experimental Ophthalmology
Volume45
Issue number9
DOIs
Publication statusPublished - Dec 2017

Keywords

  • DBA/2J
  • Glaucoma
  • Mouse model

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