P215 EFFECT OF OXYGEN LOADING MODEL ON RETINOPATHY OF PREMATURITY IN INTRAUTERINE GROWTH RETARDED MICE

Background and Objective: Fetal growth retardation (IUGR) not only induces various complications in newborns, but is also known to be associated with the future development of lifestyle-related diseases and conditions. Therefore, the neonatal treatment often struggles between life-sustaining and oxygen administration. We have previously reported that IUGR mice born from mothers raised on a low-protein diet show enhanced vascular remodeling. The mechanism is influenced by an increased inflammatory response associated with a decreased angiogenic response due to hypoxic loading in a femoral artery cuff implantation model. Based on this, we hypothesized that in IUGR mice, the reduced angiogenic response in retinopathy of prematurity may work to suppress the onset of the disease. To test this hypothesis, we examined the effects of oxygen loading on the retinal neovasculature using the mouse oxygen-induced retinopathy of prematurity (OIR) model. Methods The OIR model was created in newborns born from mothers raised on a normal protein diet (20%) and in IUGR newborns born from mothers raised on a low protein diet (8%). Specifically, the newborns were exposed to 75% hyperoxia for 5 days starting at 7 days of age, and retinal neovascularization was histologically evaluated 5 days later at 17 days of age for comprehensive transcriptome analysis. Results: Compared to normal birth weight OIR mice, retinal neovascularization was significantly suppressed in OIR mice with FGR. Retinal RNA sequencing revealed decreased expression of angiogenic factors that trigger pathological retinal neovascularization, such as the mitogen-activated protein kinase pathway (MAPK) pathway and corresponding upstream signaling pathways. Conclusions Our findings suggest that IUGR neonates have a weaker response to retinal oxygen stress and consequently are likely to have reduced retinopathy of prematurity. These results indicate that the risk of developing retinopathy of prematurity is attenuated in IUGR neonates compared to mature neonates with normal birth weight.