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Updated: Jun 20, 2026
Oxygen-Induced Retinopathy Model for Ischemic Retinal Diseases in Rodents
Published on: September 16, 2020
High-dose erythropoietin does not exacerbate retinopathy of prematurity in rats
Jessica D Slusarski1, Ronald J McPherson, Gerard N Wallace
1Department of Pediatrics, University of Washington, Seattle, Washington 98195, USA.
Insights
High-dose recombinant erythropoietin (rEpo) crosses the blood-eye barrier and may offer neuroprotection for preterm infants. While high-dose rEpo showed some impact on retinopathy of prematurity (ROP) in rats, lower doses did not significantly alter ROP development.
Area of Science:
- Neonatal neurology
- Ophthalmology
- Pharmacology
Background:
- Preterm infants face significant risks of brain injury.
- Recombinant erythropoietin (rEpo) is a potential therapeutic agent for neonatal brain injury.
- The impact of rEpo on retinopathy of prematurity (ROP) remains largely unknown.
Purpose of the Study:
- To investigate if rEpo crosses the blood-eye barrier.
- To determine the effect of early rEpo administration on ROP development in a rat model.
Main Methods:
- Epo concentrations were measured in plasma and eye tissue using ELISA.
- Rats were administered varying doses of rEpo or saline on postnatal days 1-3.
- Animals were exposed to room air or cyclic oxygen exposure (COE) to induce ROP.
- Retinal vascular pathology was assessed in stained retinal flat mounts.
Main Results:
- rEpo demonstrated dose- and time-dependent penetration into the eye.
- COE exacerbated retinal vascular pathology and reduced vessel density compared to room air.
- High-dose rEpo (30,000 U/kg) increased ROP scores in ADPase-stained tissues, but not with fluorescein staining.
- Low-dose rEpo (5000 U/kg) did not significantly affect ROP incidence or severity.
Conclusions:
- Early administration of high-dose rEpo can penetrate the blood-eye barrier.
- High-dose rEpo may offer neuroprotective benefits for preterm infants with minimal adverse effects on ROP development.
- Lower doses of rEpo appear to have no significant impact on ROP in this model.
Abstract:
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.
