June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
Sub-chronic IOP lowering effect of AMA0076 and Y-39983 in Dutch Belted rabbits
Author Affiliations & Notes
  • Sarah Van de Velde
    Lab of Ophthalmology, KULeuven, Leuven, Belgium
  • Tine Van Bergen
    Lab of Ophthalmology, KULeuven, Leuven, Belgium
  • Davine Sijnave
    Lab of Ophthalmology, KULeuven, Leuven, Belgium
  • Karolien Hollanders
    Lab of Ophthalmology, KULeuven, Leuven, Belgium
  • Evelien Vandewalle
    Lab of Ophthalmology, KULeuven, Leuven, Belgium
  • Lieve Moons
    Biology, Zoölogical Institute, KULeuven, Leuven, Belgium
  • Dirk Leysen
    Amakem Therapeutics, Diepenbeek, Belgium
  • Ingeborg Stalmans
    Lab of Ophthalmology, KULeuven, Leuven, Belgium
  • Footnotes
    Commercial Relationships Sarah Van de Velde, Amakem Therapeutics (F); Tine Van Bergen, None; Davine Sijnave, Amakem therapeutics (F); Karolien Hollanders, None; Evelien Vandewalle, None; Lieve Moons, None; Dirk Leysen, Amakem NV (E); Ingeborg Stalmans, Amakem (F), Amakem (C), Amakem (R)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 5631. doi:https://doi.org/
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      Sarah Van de Velde, Tine Van Bergen, Davine Sijnave, Karolien Hollanders, Evelien Vandewalle, Lieve Moons, Dirk Leysen, Ingeborg Stalmans; Sub-chronic IOP lowering effect of AMA0076 and Y-39983 in Dutch Belted rabbits. Invest. Ophthalmol. Vis. Sci. 2013;54(15):5631. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: To investigate IOP lowering efficacy of rho kinase (ROCK) inhibitors, AMA0076 and Y-39983, after sub-chronic treatment.

Methods: Dutch Belted rabbits (5 rabbits/concentration) were treated daily with a single topical dose of AMA0076 (0.05, 0.1 and 0.4%) or Y-39983 (0.025, 0.05 and 0.1%) in a masked fashion for 14 days. Saline was used as control in the contralateral eye. IOP was measured before, 3 and 7 hours after administration of the treatment. AMA0076 is a locally acting ROCK inhibitor, developed by Amakem Therapeutics, to reduce side effects such as hyperemia otherwise seen after administration of a ROCK inhibitor.

Results: Mean baseline IOP before the start of the experiment (day 0) was 21.02 ± 0.42 and 20.69 ± 0.39 mmHg for AMA0076 and Y-39983, respectively. Significant IOP reduction was observed in all AMA0076 and Y-39983 treatment groups. A maximal IOP reduction of 39 and 35% was reached with AMA0076 0.1% and Y-39983 0.05%, respectively. Initially, IOP returned to baseline values (day 0) 24 hours after administration of AMA0076. After 3 days of treatment with AMA0076 a sustained IOP lowering effect was present, IOP did not return to baseline values (day 0), but remained significantly lower for all concentrations of AMA0076 (p<0.05). Treatment with Y-39983 did not show this sustained IOP decrease. As a result of this sustained IOP lowering effect smaller IOP fluctuations were observed in animals treated with AMA0076 compared to Y-39983. Hyperemia was observed with all concentrations of Y-39983 whereas only mild hyperemia was induced after administration of AMA0076 0.4% (highest concentration used).

Conclusions: Once daily treatment of rabbits with ROCK inhibitor AMA0076 resulted in IOP reduction that was more sustained and associated with smaller peak-trough fluctuations than Y-39983.

Keywords: 568 intraocular pressure  
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