A new study published by The University of Utah’s John A. Moran Eye Center highlights significant progress toward isolating the underlying causes of retinopathy of prematurity (ROP), a condition that commonly affects prematurely born babies who have received intensive neonatal care.
Through this study, researchers are closer to suppressing effects from specific cells that overproduce vascular endothelial growth factor (VEGF), a signaling protein that promotes blood vessel growth and is essential to the development of not only the retina, but also other organs in human infants, including the brain, kidney, and lungs. Overproduction of VEGF could lead to blindness in pre-term infants.
The study, which is published in the September issue of the American Journal of Pathology, also uses rats, not mice, in a more representative study model of human ROP in pre-term infants. But it proposes modifying the rat oxygen-induced retinopathy (OIR) model using gene delivery approaches which will allow researchers to regulate the production of VEGF to combat ROP without negatively compromising other prenatal growth.
"With this study, we have found a way to use molecular methods to safely control VEGF as opposed to completely blocking it, which will help combat the negative effects of broad inhibitors when they have access to the blood stream," said Mary Elizabeth Hartnett, MD, principal investigator at the Moran Eye Center’s Retinal Angiogenesis Laboratory and senior investigator of the research paper. "We don’t propose gene therapy for human preterm infants, but this research is the first step needed to start identifying the specific receptors that are stimulated when VEGF is overproduced, which will ultimately help us find safe and effective treatments for ROP."
ROP is in part caused from abnormal blood vessel growth that occurs from too much production of VEGF. Using broad inhibitors to block VEGF can reduce the risk of ROP in human infants, but also may then prohibit the necessary growth of other vital organs such as the brain, kidneys, and lungs.
As it is unsafe to study fragile human preterm infant eyes to understand ROP, researchers typically use a mouse model of OIR to examine the production of VEGF and for the development of treatment options. Using a rat OIR model is actually more representative of human ROP, but using this model requires pharmacological manipulations that do not determine specific cells that overproduce VEGF or how VEGF causes growth of abnormal, instead of normal, blood vessels. Use of molecular methods improves the rigor of the model and also targets pathologic pathways while sparing normal pathways.
Funded by the National Eye Institute (grant EY015130), the study involved researchers from the Department of Ophthalmology and Cell Biology and Physiology at the University of North Carolina, Chapel Hill, the Helen Wills Neuroscience Institute at the University of California, Berkeley and Spiral Devices, LLC in addition to the John A. Moran Eye Center at the University of Utah.