June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Neuroprotective evaluation of topically delivered trabodenoson in an acute ischemic rodent model
Author Affiliations & Notes
  • James A Gow
    Inotek Pharmaceuticals, Lexington, Massachusetts, United States
  • Craig E Crosson
    Ophthalmology, Medical University of South Carolina, Charleston, South Carolina, United States
  • David Albers
    Inotek Pharmaceuticals, Lexington, Massachusetts, United States
  • Cadmus C Rich
    Inotek Pharmaceuticals, Lexington, Massachusetts, United States
  • Rudolf Baumgartner
    Inotek Pharmaceuticals, Lexington, Massachusetts, United States
  • Footnotes
    Commercial Relationships   James Gow, Inotek Pharmaceuticals (E); Craig Crosson, Inotek Pharmaceuticals (C); David Albers, Inotek Pharmaceuticals (E); Cadmus Rich, Inotek Pharmaceuticals (E); Rudolf Baumgartner, Inotek Pharmaceuticals (E)
  • Footnotes
    Support  Inotek Pharmaceuticals
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 5898. doi:
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      James A Gow, Craig E Crosson, David Albers, Cadmus C Rich, Rudolf Baumgartner; Neuroprotective evaluation of topically delivered trabodenoson in an acute ischemic rodent model. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5898.

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

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Abstract

Purpose : Trabodenoson, an adenosine mimetic highly selective for the A1 receptor, has been reported to lower IOP in humans with glaucoma (Myers et al (2016) JOPT 32, 555). As the stimulation of adenosine A1 receptors has been shown to be neuroprotective in several systems, we sought to evaluate whether topical (ocular) delivery of trabodenoson can protect the retina from acute ischemic injury.

Methods : Male Brown Norway rats received unilateral ischemic injury (IOP elevated to 160 mmHg for 45 min) on Day 0. The contralateral eye from each animal served as control. Full field scotopic ERGs were recorded on the day prior to ischemia (Day -1) and 7 days post-ischemic injury. Treated animals received ocular (topical) drops of 6% trabodenoson (5 ml) bilaterally starting 2 hrs prior to ischemic injury (Day 0), and then twice daily on Study Days 1 through 7. Treated animal were compared to untreated control animals.

Results : In control animals, ERG analysis of ischemic eyes 7 days post-injury demonstrated that mean a- and b-wave amplitudes were significantly reduced from baseline values by 49 ± 6% and 60 ± 7%, respectively. In trabodenoson-treated animals, ERG analysis of ischemic eyes demonstrated that mean a- and b-wave amplitudes were reduced from baseline values by 29 ± 4% and 30 ± 5%, respectively. Comparing corresponding eyes from control and trabodenoson-treated animals revealed that trabodenoson treatment significantly (p<0.05) preserved inner retinal function as measured by increased b-wave amplitude. A trend toward preservation of photoreceptor function was measured as an increase in a-wave amplitude. No significant changes from baseline a- and b-wave amplitudes in contralateral, non-ischemic eyes from trabodenoson-treated or control animals were measured.

Conclusions : These initial results support the idea that topical (ocular) delivery of trabodenoson can protect the retina from ischemic injury. This retinal neuroprotection was primarily associated with preserving inner retinal function. Additional studies should be conducted to further validate trabodenoson’s retinal neuroprotective activity.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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