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S.S. Samudre, I.G. Castillo, A. Hosseini, F.A. Lattanzio, Jr., R.C. Allen, P.B. Williams; Development of a Stable Rat Ocular Hypertension Model . Invest. Ophthalmol. Vis. Sci. 2004;45(13):4448.
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Purpose: Episcleral vein ligation has been reported to induce ocular hypertension in rats. However, the duration of ocular hypertension may be as short as 5 wks, which is insufficient to mimic the effects of prolonged ocular hypertension. We hypothesized that minimizing surgical trauma, a stimulus for vascular anastomosis which returns IOP toward normal, would increase the duration of ocular hypertension. Methods: Ocular hypertension was induced in Sprague–Dawley (n=21) and Brown Norway (n=4) rats. After anesthetization a 5 mm lateral canthotomy was performed. Conjunctival dissection was limited to the immediate area around 3 vortex veins, which were ligated with 9.0 nylon suture. The contralateral eye served as a control. Before surgery, baseline intraocular pressure (IOP) was measured using Goldman applanation tonometry and weekly post–operatively. The criteria for ocular hypertension were a consistent difference >5 mmHg between eyes. Results: In Sprague–Dawley rats, pre–surgical IOP (12.0±0.5 mmHg) was not different from the contralateral eye (11.1±0.8 mmHg). Within 7 d, IOP increased by 4.2±2.3 mmHg in 20 of 21 rats. After 4 wks IOP increased by 5.1±0.9 mmHg in the operated eye (p14 weeks (13/14 rats, p5 mmHg difference for >25 wks. Timolol (0.5%) reduced IOP by 7.0±1.1 mmHg for >120 min minimizing the difference between treated and untreated eyes to 1.1±0.2 mmHg. Brown Norway rats required 6 wks to meet hypertensive criteria, an increase of 5.1±0.6 mmHg (p<0.05). After 15 weeks, the difference between eyes was 7.8±0.2 mmHg (p<0.05). Timolol (0.5%) reduced IOP by 3.5±0.3 mmHg for 60 min; the difference between eyes was 2.4±0.3 mmHg. In other experiments, a similar surgical intervention in Long Evans rats evelated IOP to 33.4±1.3 mmHg (n=53) but the increased IOP was not sustained. Conclusions:By minimizing surgical trauma, a consistent, long–term, inexpensive rat ocular hypertensive model was developed. Ocular hypertension developed in >95% of rats. Although the model was successful in three strains of rats, there were differences between them. IOP elevation has been maintained for up to 36 weeks. IOP increased more rapidly in the Sprague–Dawley rats. Timolol decreased IOP by 50% in Sprague–Dawley rats but only by 28% in Brown Norway rats.
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