High-dose erythropoietin does not exacerbate retinopathy of prematurity in rats.
Preterm infants are at high risk of brain injury, and high-dose recombinant erythropoietin (rEpo) may be therapeutic. However, the effect of rEpo on the development of retinopathy of prematurity (ROP) is unknown. We hypothesized that (1) rEpo would cross the blood-eye barrier and (2) early rEpo would modulate ROP in a rat model. Epo concentrations were measured by ELISA from the plasma and the homogenized eye tissue at timed intervals after rEpo injection. Flat-mounted retinas were prepared from rats given rEpo (0, 5000, or 30,000 U/kg i.p. qid x 3) on postnatal d (P) 1-3 that were raised in room air (RA) or cyclic oxygen exposure (COE) with O2 cycling every 24 h between 50% and 10% for 14 d. Photomicrographs of the fluorescein- or ADPase-stained P20 retinas were examined. rEpo penetrated into the eye in a dose- and time-dependent manner. COE increased retinal vascular pathology and decreased vessel density compared with RA controls. The 30,000 U/kg dose of rEpo increased the ROP clock hour scores, but only in ADPase-stained tissues. In contrast, 5000 U/kg rEpo did not change the incidence or severity of ROP by any measure. High-dose rEpo may protect against preterm brain injury with minimal impact on ROP.
Slusarski
Jessica D
JD
Department of Pediatrics, University of Washington, Seattle, Washington 98195, USA.
McPherson
Ronald J
RJ
Wallace
Gerard N
GN
Juul
Sandra E
SE
D000704:Analysis of Variance; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D004921:Erythropoietin / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D005451:Fluorescein Angiography; D006801:Humans; D007231:Infant, Newborn; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000009:adverse effects*; D010100:Oxygen / Q000633:toxicity; D051381:Rats; D011994:Recombinant Proteins; D012160:Retina / Q000187:drug effects*; D012178:Retinopathy of Prematurity / Q000139:chemically induced*
D018696:Neuroprotective Agents; D011994:Recombinant Proteins; D004921:Erythropoietin; D010100:Oxygen