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Updated: Jun 5, 2026
Intravitreal Injections in the Ovine Eye
Published on: July 5, 2022
Erythropoietin protects the developing retina in an ovine model of endotoxin-induced retinal injury
Michelle M Loeliger1, Anna Mackintosh, Robert De Matteo
1Department of Anatomy and Cell Biology, University of Melbourne, Parkville, Victoria, Australia.
Insights
Recombinant human erythropoietin (rhEPO) protected fetal retinas from inflammation-induced injury in a sheep model. This neuroprotective therapy may prevent visual deficits in preterm infants born after intrauterine infection.
Area of Science:
- Neuroscience
- Ophthalmology
- Developmental Biology
Background:
- Intrauterine infection is a primary cause of preterm birth.
- Preterm infants face high risks of neurologic and visual impairments.
- Therapeutic strategies are needed to mitigate adverse outcomes in very preterm neonates.
Purpose of the Study:
- To investigate the neuroprotective effects of recombinant human erythropoietin (rhEPO) on retinal injury.
- To assess rhEPO's efficacy in an ovine model of intrauterine inflammation-induced retinal damage.
Main Methods:
- Fetal sheep at 107 days gestational age received lipopolysaccharide (LPS) to induce inflammation, with or without rhEPO treatment.
- Physiological parameters were monitored throughout the study.
- Retinal morphology and neurochemistry were quantitatively assessed at 116 days gestational age.
Main Results:
- LPS exposure caused fetal hypoxemia, hypotension, and significant retinal alterations.
- Retinal damage included reduced inner nuclear layer thickness and fewer ganglion cells.
- rhEPO treatment mitigated these retinal changes without altering LPS's physiological effects.
Conclusions:
- rhEPO demonstrates significant neuroprotective benefits for the developing retina following inflammatory insult.
- Potential mechanisms include EPO's anti-apoptotic and anti-inflammatory properties.
- rhEPO may be a viable therapeutic option for preventing visual deficits in preterm infants exposed to intrauterine inflammation.
Purpose:
Intrauterine infection is a common antecedent of preterm birth. Infants born very preterm are at increased risk for neurologic dysfunction, including visual deficits. With increasing survival of very preterm infants, there is a need for therapies that prevent adverse neurologic outcomes. Using an ovine model, the authors investigated the neuroprotective potential of recombinant human erythropoietin (rhEPO) on retinal injury induced by intrauterine inflammation.
Methods:
At 107 ± 1 days of gestational age (DGA), chronically catheterized fetal sheep received either of the following on 3 consecutive days: intravenous (IV) bolus dose of lipopolysaccharide (LPS; ∼0.9 μg/kg; n = 8); IV bolus dose of LPS, followed at 1 hour by 5000 IU/kg rhEPO (LPS + rhEPO; n = 8); rhEPO alone (n = 5). Untreated fetuses (n = 8) were used for comparison with the three treatment groups. Fetal physiological parameters were monitored. At 116 ± 1 DGA, fetal retinas were assessed quantitatively for morphologic and neurochemical alterations.
Results:
Exposure to LPS alone, but not to rhEPO alone, resulted in fetal hypoxemia and hypotension (P < 0.05). Exposure to LPS alone caused retinal changes, including reductions in thickness of the inner nuclear layer (INL), somal areas of INL neurons, process growth in the plexiform layers, and numbers of ganglion and tyrosine hydroxylase immunoreactive (TH-IR) dopaminergic amacrine cells. Treatment of LPS-exposed fetuses with rhEPO did not alter the physiological effects of LPS but significantly reduced alterations in retinal layers and ganglion and TH-IR cell numbers.
Conclusions:
rhEPO treatment was beneficial in protecting the developing retina after LPS-induced inflammation. Retinal protection could occur by the antiapoptotic or anti-inflammatory actions of EPO.
