AI Article Synopsis
- Phlebotomy-induced-anemia (PIA) in neonatal rats is examined for its effects on retinopathy of prematurity (ROP), revealing that PIA may actually decrease the severity of the condition rather than worsen it as initially hypothesized.* -
- In the study, PIA resulted in a significant decrease in avascular and neovascular areas of the retina, as well as lower levels of several pro-inflammatory cytokines at key developmental stages (P15 and P20).* -
- Findings suggest that anemia has a protective effect against pathological retinal changes in ROP, influencing gene expression and molecular pathways associated with angiogenesis and inflammation, with notable differences observed based on the sex of the subjects.*
Article Abstract
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.
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| http://dx.doi.org/10.1038/s41390-024-03477-w | DOI Listing |
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