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Bang V Bui, Da Zhao, Christine Tram Oanh Nguyen, Jeremiah K.H. Lim, Holly Rose Chinnery, Algis J Vingrys, Zheng He; Circumlimbal suture chronic intraocular pressure elevation in mice. Invest. Ophthalmol. Vis. Sci. 2016;57(12):2524.
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© ARVO (1962-2015); The Authors (2016-present)
To assess the effect of 12-weeks of mild chronic IOP elevation, induced by a circumlimbal suture, on the structure and function of the mouse retina.
Anesthetized (60:5mg/kg ketamine:xylazine) adult C57BL6/J mice (n=10) had a unilateral circumlimbal suture (12/0) applied around the equator of the eye for 12 weeks. The contralateral eye was left untreated as control. IOP was measured using a rebound tonometer immediately after (2min, 1hr, 2hr), then once a day for the first 3 days and twice a week thereafter. After 12 weeks, electroretinograms (ERG) were measured to assess photoreceptor (P3), bipolar cell (P2) and retinal ganglion cell (positive scotopic threshold response, pSTR) activity. Amplitudes have been expressed relative (average%±SEM) to the contralateral untreated control eye. Following ERG assessment, flat mount retinae were stained with RNA binding protein with multiple splicing (RBPMS) to identify ganglion cells. Cell counts were undertaken in both central (0.3mm from optic nerve) and peripheral (0.3mm from retinal-ciliary body border) locations in all retinal quadrants.
Immediately after suture, IOP spiked at 33±3 mmHg to peak at 42±4 mmHg by 1 hr. After 1 day, IOP had dropped to 27±3 mmHg. From weeks 2 to 12, IOP remained significantly elevated above baseline (control 12±1 mmHg, treated 18±1 mmHg, p<0.01). IOP in control eyes remained normal throughout the experiment (p > 0.05). After 12 weeks of chronic IOP elevation there was a significant reduction in the amplitude of photoreceptor (-18±5%, p<0.01), bipolar cell (-19±6%, p<0.01) and ganglion cell dominant responses (-32±14%, p=0.02). There was a modest correlation between summed IOP (weeks 1 to 12) and pSTR loss (p=0.04, r=0.58). Ganglion cell density was reduced in the central retina (92.1±4.8%, but not in the periphery (99.3±5.4%) with a significant reduction in the central, temporal quadrant (90.0±2.9%). Average ganglion cell density across all quadrants was correlated with pSTR amplitude (p=0.03, r=0.61).
Circumlimbal ligation produces mild chronic ocular hypertension in mice. Deficits are found in all retinal ERG responses after 12-weeks, with a trend for a greater deficit in ganglion cell responses. This model may have utility in glaucoma research.
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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