July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Post-trauma therapy with microparticle-mediated delivery of erythropoietin
Author Affiliations & Notes
  • Alexandra Bernardo Colon
    Ophthalmology & Visual Science, Vanderbilt Medical Center, Nashville, Tennessee, United States
  • Sarah Naguib Naguib
    Ophthalmology & Visual Science, Vanderbilt Medical Center, Nashville, Tennessee, United States
  • Megan M. Erwin
    Ophthalmology & Visual Science, Vanderbilt Medical Center, Nashville, Tennessee, United States
  • Taylor Kavanaugh
    Biomedical Engineering, Vanderbilt University, Nashville, Tennessee, United States
  • Mukesh Gupta
    Biomedical Engineering, Vanderbilt University, Nashville, Tennessee, United States
  • Craig Duvall
    Biomedical Engineering, Vanderbilt University, Nashville, Tennessee, United States
  • Tonia S Rex
    Ophthalmology & Visual Science, Vanderbilt Medical Center, Nashville, Tennessee, United States
  • Footnotes
    Commercial Relationships   Alexandra Bernardo Colon, None; Sarah Naguib Naguib, None; Megan M. Erwin, None; Taylor Kavanaugh, None; Mukesh Gupta, None; Craig Duvall, None; Tonia Rex, None
  • Footnotes
    Support  NEI R01 EY022349 (TR), DoD W81XWH-15-1-0096 (TR) and W81XWH-17-2- 0055 (TR), NIA R01 NS094595 (TR), Potocsnak Discovery Grant in Regenerative Medicine (TR), Ayers Foundation Regenerative Visual Neuroscience Pilot Grant (TR), VA I01 CX001610-01 (FH), NIH R01EY024997 (DC) and P30EY008126 (DC), the Glaucoma Research Foundation (DC), the Stanley Cohen Innovation Fund (DC), and the Vanderbilt University Medical Center Cell Imaging Shared Resource core facility (Clinical and Translational Science Award Grant UL1 RR024975 from National Center for Research Resources), Training Grant in Vision Research T32 EY021833, Research Prevent Blindness, Inc.
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 4406. doi:https://doi.org/
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      Alexandra Bernardo Colon, Sarah Naguib Naguib, Megan M. Erwin, Taylor Kavanaugh, Mukesh Gupta, Craig Duvall, Tonia S Rex; Post-trauma therapy with microparticle-mediated delivery of erythropoietin. Invest. Ophthalmol. Vis. Sci. 2019;60(9):4406. doi: https://doi.org/.

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

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Abstract

Purpose : Our goal was to assess the effect of sustained intraocular delivery of a non-erythropoietic form of erythropoietin (EPO-R76E) after ocular trauma.

Methods : We exposed one eye of an anesthetized C57Bl/6 mouse to 2 bursts of overpressure air (15psi) for three consecutive days [(2X15PSI) x3]. Sham mice were anesthetized and placed into the air blast system, but were not exposed to the overpressure air. One day after the last blast mice were intravitreally (IVT) injected with: saline, and empty or EPO-R76E-containing poly-propylene sulfide (PPS) microparticles. One month after injury visual function was measured and tissue was collected for biochemistry and histology.

Results : We detected release of EPO-R76E from the microparticles in vivo for 6 weeks after blast and a single IVT injection. Both empty and EPO-R76E-containing PPS microparticles preserved the visual evoked potential amplitude (42 ± 8.μV) and latency (45 ± 5ms), as compared to the saline blast-injured group - 20 ± 4μV and 55 ± 7ms, respectively. Similarly, the ERG bmax was preserved in the PPS microparticle treated groups. Both EPO-R76E containing and empty microparticles also prevented blast-induced increases in cleaved caspase-1 and in IL-1 α and IL-1β.

Conclusions : Treatment with empty PPS microparticles was as efficacious as EPO-R76E-containing PPS microparticles in preserving visual function and preventing the activation of the IL-1 inflammatory pathway. PPS microparticles react with and detoxify ROS, thus these data suggest that reducing ROS even a day after blast is therapeutic and that EPO-R76E may be acting primarily through blocking ROS since there was no additive protective effect of including EPO-R76E in the microparticles. More rigorous models and dose response studies may better uncover cooperative effects of PPS and EPO-R76E.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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