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Anita Jillian Turner, Roshana Vanderwall, Vivek Gupta, Alexander Klistorner, Stuart L Graham; DBA 2J mouse model for experimental glaucoma – pitfalls and problems. Invest. Ophthalmol. Vis. Sci. 2016;57(12):5143.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: The DBA2J mouse has been described as a model for congenital experimental glaucoma. This inbred strain develops anterior segment anomalies, iris atrophy, peripheral anterior synechiae and pigment dispersion leading to raised intraocular pressure (IOP) and glaucomatous damage as well as corneal, heart and major vessel calcification. We used this model to determine the effects of a neuroprotective agent during development of glaucoma and found that it was difficult to assess the progression of the disease due to the abovementioned abnormalities.
Methods: We followed 52 mice from 12 weeks to 12 months of age and evaluated iris changes, corneal calcification, intraocular pressure – iCare tonometer, retinal electrophysiology, and retinal structure with optical coherence tomography (OCT) and correlated findings with histology.
Results: Iris changes became apparent from 6m whereby pupil dilation was limited or deformed. Corneal calcification developed as early as 12 weeks, all mice displayed significant calcification by 6m. In controls, mean IOP was 8.4 ± 0.2mmHg at 3m and did not begin to increase until 9m (mean 13.8 ± 0.9mmHg; range 8.3 – 27.0). By 12m some mice showed little IOP elevation (mean 19.0 ± 1.4 mmHg; range 8.0 – 27.3) despite substantial iris changes. We believe that the IOP measurements may be inaccurate due to extensive corneal calcification. Longitudinal OCT imaging indicated progressive thinning of the RGC layer, cupping at the optic nerve head and INL damage in many eyes however several mice exhibiting these changes did not have elevated IOP. It was often difficult to obtain OCT images due to corneal calcifications and pupil abnormalities. Mean STR was decreased (90uV at 3m; 35uV at 12m) with a minor change in ERG (472uV at 3m; 448uV at 12m) possibly due to the lack of pupil dilation. During the study a total of 20 mice died due to cardiac calcification (13), thoracic cavity malformation (2), bladder obstruction (2), aortic aneurysm (1), other causes (2).
Conclusions: This model presents serious problems with corneal calcification affecting the ability to accurately assess IOP and to obtain OCT images. Due to the variable time to onset and degree of IOP elevation, planning interventional trials of therapeutic agents is difficult. In addition, the high rate of systemic complications leading to cardiovascular dysfunction and death is a complicating factor.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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