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Jessica Hines-Beard, Lauren D'Surney, Brendan Lunn, Courtney Bricker-Anthony, Tonia Rex; Delayed treatment with erythropoietin protects against ocular trauma. Invest. Ophthalmol. Vis. Sci. 2013;54(15):729. doi: https://doi.org/.
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The goal of this study was to determine if erythropoietin (EPO) is an effective neuroprotective treatment for retinal injury due to ocular trauma.
Three month old DBA/2J mice received either a 26psi or 0psi blast to the left eye only with contralateral eyes serving as internal controls. Gross pathology and intraocular pressure (IOP) measurements were collected prior to and immediately, 3 days, and 7 days after blast exposure. Intraperitoneal (IP) injections of EPO or PBS were administered either immediately, 6 hours, or 24 hours after trauma followed by additional doses 24 and 48 hours after intial treatment. Eyes were harvested 7 days after blast. Cryo-embedded sections were labeled with anti-GFAP and TUNEL to detect neuronal stress and retinal cell death, respectively. TUNEL-positive cells were counted and GFAP-positive processes were measured along with the region of retina affected.
Corneal edema was present in approximately 50% of control and EPO 0h and 6hr groups. In contrast, no edema was detected in mice in the EPO 24 hr group. GFAP labeling was increased with processes extending into the outer nuclear layer in the buffer control and 0 hr EPO groups that encompassed approximately 70% of the retina. The EPO 6 hr group had GFAP -positive processes extending to the inner plexiform layer and spanned approximately 60% of the retina. In contrast, the 24 hour EPO group had many fewer processes extending into the retina and only approximately 25% of the retina was affected. The 0psi blast control group had no GFAP upregulation. The control and EPO 0 hr groups had TUNEL positive cells across 20% of the mid-peripheral and central retina. The EPO 6hr and 24hr groups had TUNEL-positive cells across 14% and 4% of the mid-peripheral and central retina, respectively.
Systemic treatment with EPO 24 hrs after ocular trauma resulted in decreased corneal edema, glial stress, and retinal cell death. Administration of EPO three times from 24-72 hrs after trauma was more effective than treatment from 0-48 or 6-52 hrs after ocular trauma with assessments performed 7 days post-blast. These results indicate that delayed treatment with EPO is effective, and that continued treatment with EPO may be necessary to maintain the neuroprotective effect since withdrawal of treatment for greater than four days did not yield significant neuroprotection despite an earlier onset of therapy.
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