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Laura Lorenzo-Soler, Ólöf Birna Ólafsdóttir, Íris Mýrdal Kristinsdóttir, Phatsawee Jansook, Thorsteinn Loftsson, Einar Stefánsson; Angiotensin II receptor blockers in nanoparticle eye drops lower IOP in rabbits. Invest. Ophthalmol. Vis. Sci. 2019;60(9):3199.
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The renin–angiotensin system is key in the physiology of hypertension, with angiotensin II binding to the angiotensin II type 1 receptor (AT1), which mediates the pathways that lead to vasoconstriction and water retention. Consistently, angiotensin II receptor blockers (ARBs), such as Irbesartan and Telmisartan, have proved to significantly reduce intraocular pressure (IOP) in mice when administered orally. However, the administration of oral IOP lowering agents may lead to systemic side-effects. Topical administration of ARBs to the eye might create a new class of IOP lowering treatment. In this study, we compare the effectiveness of two ARBs eye drops with Timolol.
Two ARBs nanoparticle eye drops formulations, 1.5% Irbesartan and 0.15% Candesartan, were studied in 10 normotensive rabbits and compared with a commercial 0.5% Timolol solution after a single dose application. Vehicle solution for ARBs was also administered to a vehicle control group. Blank control group did not receive any treatment but was likewise monitored to determine the effect on IOP.
In accord with previous studies, Timolol reached a low in IOP 2 hours after the administration, significantly decreasing from 24.9 ± 4.2 mmHg (mean ± SD) to 20.4 ± 4.8 mmHg (p=0.036, n=10). Irbesartan showed a similar outcome to Timolol, while Candesartan significantly lowered the IOP from 24.6 ± 5.1 mmHg to 19.0 ± 2.9 mmHg (p=0.030, n=10) after four hours of the administration. The IOP in the vehicle group was 20.6 ± 1.9 mmHg at baseline and 19.5 ± 3.4 mmHg 4 hours after the administration. The blank group had an initial IOP of 21.8 ± 2.3 mmHg and 4 hours later it was 19.1 ± 2.6 mmHg.
Topical application of ARBs as eye drops can reduce IOP in normotensive rabbits, showing similar effects to timolol eye drops. ARBs may represent a new class of molecules for IOP lowering treatment. Further studies including human clinical trials are needed to further evaluate this potential.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
Figure 1. IOP average change (mean ± SEM) for each study group.
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