July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Angiotensin II receptor blockers in nanoparticle eye drops lower IOP in rabbits
Author Affiliations & Notes
  • Laura Lorenzo-Soler
    Faculty of Medicine, University of Iceland, Reykjavík, Iceland
  • Ólöf Birna Ólafsdóttir
    Faculty of Medicine, University of Iceland, Reykjavík, Iceland
    Department of Ophthalmology, Landspitali University Hospital, Reykjavík, Iceland
  • Íris Mýrdal Kristinsdóttir
    Oculis ehf., Reykjavík, Iceland
  • Phatsawee Jansook
    Oculis ehf., Reykjavík, Iceland
  • Thorsteinn Loftsson
    Faculty of Pharmaceutical Sciences, University of Iceland, Reykjavík, Iceland
    Oculis ehf., Reykjavík, Iceland
  • Einar Stefánsson
    Faculty of Medicine, University of Iceland, Reykjavík, Iceland
    Oculis ehf., Reykjavík, Iceland
  • Footnotes
    Commercial Relationships   Laura Lorenzo-Soler, None; Ólöf Ólafsdóttir, None; Íris Kristinsdóttir, Oculis ehf. (E); Phatsawee Jansook, None; Thorsteinn Loftsson, Oculis ehf. (I); Einar Stefánsson, Oculis ehf. (I)
  • Footnotes
    Support  Supported by H2020 Marie Curie grant
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 3199. doi:
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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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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : 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.

Methods : 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.

Results : 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.

Conclusions : 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.

Figure 1. IOP average change (mean ± SEM) for each study group.

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