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Cristos Ifantides, Peggy Borum, Christina McGowan, W Clay Smith; A Novel ROP Model in Premature Piglets. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5387.
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Retinopathy of Prematurity (ROP) occurs in 16% of all premature births. It is a major cause of blindness in both the developed and developing world, making it an important area of interest for research. ROP studies have been conducted in different animal models, including the mouse, rabbit, and kitten, but no published research is present in piglets. Porcine retinal vasculature closely resembles that of the human, making it an ideal animal model to study retinal vasculature pathology. We set out to create the first successful ROP piglet model that would demonstrate characteristics of immature retinal development, including increased expression of vascular endothelial growth factor (VEGF).
A Piglet Neonatal Intensive Care Unit (PNICU) that simulates a Neonatal Intensive Care Unit was employed for this study. Piglets were kept alive in incubators with ventilator support with pulse oximeter monitoring, blood gas, and electrolyte monitoring. Neonatal parenteral nutrition pump and solution was also employed and 24 hour nursing intensive care was utilized. Full term gestation for piglets is approximately 114 days. Gravid pigs underwent cesarean at 101 and 99 days days gestation (comparable to 35 weeks gestation in human neonates). Two of the piglets were kept alive on life support for 6 and 9 days. This included hyperoxia and hypoxia states. Three that perished at birth were used as controls. The eyes were enucleated, fixed, and sectioned using a cryostat. Immunohistochemistry was used to investigate VEGF in the retina. Distance to the ora serrata was also measured nasally and temporally in each specimen. Unpaired T-tests were used to compare the ROP animal model subjects to the control non-ROP animal model.
Nasal ora serrata measurements were found not to be statistically different when comparing ROP to non-ROP animal models (p=0.1972). Temporal ora serrata measurements were found not to be statistically different when comparing ROP to non-ROP animal models (p=0.4521). VEGF expression was found to be statistically different when comparing ROP to non-ROP animal models (p=0.0369).
This is the first time a piglet ROP model has been developed. Our model exhibited similar signaling protein characteristics as human ROP eyes, as well as other proliferative retinopathy animal models. In the future, this model could be used to further identify other signal proteins and may be used for investigative therapies targeting ROP.
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