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Updated: May 6, 2026
Assessment of Vascular Regeneration in the CNS Using the Mouse Retina
Published on: June 23, 2014
Phlebotomy-induced anemia reduces oxygen-induced retinopathy severity and dampens retinal developmental
Ellen C Ingolfsland1, Mandkhai Molomjamts2, Ann Foster2
1Department of Pediatrics, Division of Neonatology, University of Minnesota Medical School, Minneapolis, MN, USA. eingolf@umn.edu.
Insights
Phlebotomy-induced anemia (PIA) unexpectedly reduced retinopathy of prematurity (ROP) severity in a rat model. This study reveals PIA decreases neovascularization and dampens key molecular pathways, suggesting a protective effect against ROP.
Area of Science:
- Ophthalmology
- Neonatal Research
- Hematology
Background:
- Phlebotomy-induced anemia (PIA) is common in premature infants at risk for retinopathy of prematurity (ROP).
- PIA causes tissue hypoxia and stimulates angiogenesis.
- The study investigated if PIA exacerbates ROP's pathologic retinal neovascularization.
Purpose of the Study:
- To determine the effect of PIA on the severity of oxygen-induced retinopathy (OIR) in a neonatal rat model.
- To investigate the molecular mechanisms underlying PIA's impact on retinal neovascularization and development.
Main Methods:
- Neonatal rats were subjected to the 50/10 OIR model and induced PIA (hematocrit 18%).
- Retinal vascular morphometry, cytokine/chemokine levels, and transcriptomes were analyzed at postnatal days 15 and 20.
- Gene expression of angiogenic and iron-deficiency markers was compared between PIA and control groups.
Main Results:
- PIA decreased avascular area by 35% at P15 and neovascular area by 42% at P20 in OIR rats.
- PIA reduced pro-inflammatory cytokine/chemokine concentrations and increased mRNA for angiopoietin 2, VEGF-A, transferrin, and transferrin receptor at P20.
- RNA sequencing revealed dampened angiogenesis, inflammation, and neural development pathways, particularly in anemic OIR females.
Conclusions:
- Contrary to the hypothesis, PIA decreased OIR severity and associated retinal inflammatory markers.
- PIA dampened transcriptomic pathways crucial for retinal vascular and neural development in neonatal rats.
- These findings suggest PIA may offer a protective effect against OIR, with a notable sex-specific transcriptomic response observed.
Background:
Phlebotomy-induced-anemia (PIA), which induces tissue hypoxia and angiogenesis, occurs universally among infants at risk for severe retinopathy of prematurity (ROP). We hypothesized that PIA exacerbates pathologic retinal neovascularization in ROP.
Methods:
We induced PIA to a hematocrit of 18% among rats undergoing the established 50/10 oxygen-induced retinopathy (OIR) model. Rats were euthanized at P15 and P20, during the avascular and neovascular phases of OIR, respectively. Retinal vascular morphometry, cytokine/chemokine concentrations, transcriptomes, and mRNA expression of angiogenic and iron-deficiency markers were compared to non-PIA controls.
Results:
In OIR, PIA decreased percent avascular area at P15 by 35%, percent neovascular area at P20 by 42%, and select pro-inflammatory cytokine/chemokine concentrations at both time points. At P20, PIA increased mRNA expression of angiopoietin 2/ vascular endothelial growth factor-A 2-fold and transferrin and transferrin receptor 5-fold. RNA sequencing showed dampened pathways of angiogenesis, inflammation, and neural development in anemic OIR females.
Conclusion:
Contrary to our hypothesis, PIA decreased OIR severity and retinal cytokine and chemokine levels and dampened transcriptomic pathways central to retinal vascular and neural development in neonatal rats. These data suggest PIA provides a protective effect from OIR. Further investigation into the functional effect of these molecular changes is warranted.
Impact:
This is the first preclinical study to investigate the impact of neonatal anemia on oxygen-induced retinopathy (OIR) outcomes. This study adds to the literature that anemia decreases neovascularization, decreases cytokine and chemokine levels, and dampens angiogenic and neural transcriptomic pathways in the rat 50/10 OIR model. The study identifies a sex-specific transcriptomic response to anemia in the 50/10 OIR model, with females primarily impacted.
