September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Changes in intraocular pressure and conventional outflow hydrodynamics following acute topical administration of trabodenoson in living mice.
Author Affiliations & Notes
  • David S Albers
    Inotek Pharmaceuticals, Lexington, Massachusetts, United States
  • Guorong Li
    Duke University, Durham, North Carolina, United States
  • William K McVicar
    Inotek Pharmaceuticals, Lexington, Massachusetts, United States
  • W Daniel Stamer
    Duke University, Durham, North Carolina, United States
  • Footnotes
    Commercial Relationships   David Albers, Inotek Pharmaceuticals (E); Guorong Li, Inotek Phamaceuticals (F); William McVicar, Inotek Pharmaceuticals (E); W Stamer, Inotek Pharmaceuticals (F)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 4674. doi:
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      David S Albers, Guorong Li, William K McVicar, W Daniel Stamer; Changes in intraocular pressure and conventional outflow hydrodynamics following acute topical administration of trabodenoson in living mice.. Invest. Ophthalmol. Vis. Sci. 2016;57(12):4674.

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

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Abstract

Purpose : Trabodenoson is a selective adenosine A1 mimetic previously shown to lower intraocular pressure (IOP) in rabbits, monkeys and humans. The purpose of the current study was to determine the relationship between trabodenoson-induced changes in IOP and functional and morphological changes in outflow hydrodynamics in living mice.

Methods : C57 male and female mice received daily topical administration of 3% trabodenoson in the right eye, vehicle in the left eye (Group 1), or vehicle in both eyes (Group 2). In both groups of mice, IOPs were measured daily in both eyes by rebound tonometry, 30 min prior to drug/vehicle administration. On days 2, 4, and 7 after initiation of treatment, two cohorts of mice were culled for functional and morphological assessment: 1) Fluorescent tracer beads were perfused in living eyes prior to fixation and analyzed by immunofluorescence microscopy of anterior chamber flat mounts 2) Sagittal sections of enucleated eyes were analyzed by toluidine blue staining and light microscopy.

Results : A significant lowering in IOP was observed in trabodenoson-treated eyes as compared to vehicle-treated eyes after 7 days of treatment, decreasing IOP up to 3.7±0.38 SEM mmHg as compared to vehicle (p<0.05). Results from the tracer perfusion experiments indicate increased fluorescent signal within the trabecular meshwork from trabodenoson-treated eyes by 151% ± 28% as compared to vehicle-treated eyes after 7 days of treatment. No gross differences in morphology of conventional outflow structures were observed between trabodenosen-treated and control mice.

Conclusions : Similar to other adenosine mimetics that target the A1 receptor, topical ocular trabodenoson dosing lowers IOP in mice, increasing flow through the conventional outflow pathway.

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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