Post-trauma therapy with microparticle-mediated delivery of erythropoietin

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 b_max 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.