• Researchers Used Rigorous Model Representative of ROP to Study the Role of Erythropoietin Signaling in Retinopathy of Prematurity
• Results Pose Possibility for Decreasing ROP Severity Without Adversely Affecting Other Preterm Development
• ROP is a Leading Cause of Childhood Blindness Worldwide
The American Journal of Pathology, the leading global forum for reporting quality original research on cellular and molecular mechanisms of disease, has published a research paper originating from the John A. Moran Eye Center examining the role of erythropoietin (EPO) signaling in retinopathy of prematurity (ROP).
ROP is a leading cause of blindness worldwide, and common to most forms of ROP is the over activation of vascular endothelial growth factor (VEGF) signaling, which can cause disordered blood vessel growth. However, VEGF plays a vital role in the development of the retina and other organs in developing preterm infants, so Moran researchers focused this research on discovering mechanisms to regulate VEGF signaling without adversely reducing its beneficial effects.
Researchers used the rat oxygen-induced retinopathy (OIR) model, the most representative model of human ROP, to study the role of EPO signaling in ROP. EPO has been given to preterm infants to combat anemia and is being considered as a neuroprotective agent, but there are studies that suggest it is associated with the development of ROP. Using the OIR model, researchers found that EPO receptors were activated even when EPO was not increased, and that increased VEGF actually resulted in the activation of both EPO and VEGF receptors, which together led to pathologic angiogenesis.
³This is an exciting development, because it opens up the potential for targeting EPO receptors in endothelial cells to regulate VEGF signaling, which is dysregulated in ROP. In addition, regulation of VEGF signaling in this way could eliminate the occurrence of ROP developing if EPO is given for neural and cognitive development,² said Mary Elizabeth Hartnett, M.D., principal investigator at the Moran Eye Center¹s Retinal Angiogenesis Laboratory and corresponding author to the research paper. ³The availability of preterm infant eyes for research studies is limited, but previous research at Moran demonstrated that by using this OIR model, we can generate many of the same conditions that
preterm infants experience who develop ROP. This is just one example of how we are continually building upon the extensive research being conducted at Moran to make new and important discoveries.²
The study was funded by grant no. R01EY015130 and R01EY017011 from the National Eye Institute and supported in part by grant no. 6-FY13-75 from the March of Dimes Foundation. The study was also supported in part by an Unrestricted Grant from Research to Prevent Blindness, Inc., New York, NY, to the Department of Ophthalmology & Visual Sciences, University of Utah. To read the paper in its entirety, visit http://www.sciencedirect.com/science/article/pii/S0002944014000285.
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