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A.S. Brown, V. Cucevic, M. Zhang, F. Foster; Vascular Changes are Associated With Glaucoma Progression in DBA/2J Mice . Invest. Ophthalmol. Vis. Sci. 2006;47(13):3918.
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Vascular insufficiency is thought to contribute to ocular damage associated with glaucoma. DBA/2J mice develop spontaneous pigmentary and secondary angle–closure glaucoma. Ultrasound biomicroscopy (UBM) and micro–computed tomography (microCT) were used to quantify anterior segment angle and depth, pupil diameter, retinal blood velocity, and 3 dimensional (3D) vascular structure in DBA/2J mice from 2–12 months. Vascular modification in glaucoma progression was assessed.
UBM imaging was performed with a Vevo660 scanner (VisualSonics Inc.) at 40 MHz with 40 um resolution on DBA/2J and C57Bl/6 control mice (Jackson Laboratory) of 2–12 months of age anesthetized with isoflurane. For microCT, mice were anaesthetized with intraperitoneal ketamine (50 mg/kg) and xylazine (10 mg/kg) and transcardially perfused with Microfil® (Flow–Tech Inc.), then scanned at 80 kV, 90 kA, 11 um pixel size (model MS–8, GE Medical Systems). Ganglion cell counts were performed on 5 um H&E stained histology sections.
Iris thickening was evident at 4 months, with uneven iris pigment at 7 months, and angle closure from 9 months. Anterior chamber depth progressively increased from 2 to 12 months of age (statistical significance between 2–4 months (p=0.0003), 4–5 months (p=0.0008), 5–6 months (p=0.006), and 9–10 months (p=0.02)). Anterior segment angle measurement decreased through 12 months, statistically significant between 4–5 months (p=0.001) and 6–7 months (p=0.02). Doppler measurements indicate declining mean peak retinal blood velocity from 2 to 12 months of age, statistically significant between 8–9 months (p=0.0009). At 7 and 10 months, small areas lacking perfusion were evident in microCT of retinal vasculature, with large perfusion deficits evident at 12 months. Ganglion cell number decreased significantly between months 5–6 (p=0.004), 9–10 (p=0.002) and 10–12 (p=0.02).C57Bl/6 controls did not experience significant changes in any parameter studied.
Increasing anterior chamber depth, and decreasing pupil diameter and anterior segment angle were measured in DBA/2J mice through 12 months of age. Retinal blood velocity and perfused retinal area decreased with increasing age. Initial observations of retinal perfusion deficits occurred at 7 months of age, and retinal blood velocity significantly declined from 8–9 months. At 12 months, large perfusion–deficient areas of the retina were coincident with reductions in peak retinal blood velocity and decreased ganglion cell number, providing evidence of vascular changes during progression of the glaucomatous phenotype.
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