The Role Of Oxygen And Vascular Growth Factors And Receptor In Pathogenesis Of Retinopathy Of Neonatal Mice

PART IPurpose: To establish an optimal animal model of oxygen-induced retinopathy(OIR) suitable for examining pathogenesis and theraputic intervention for retinopathy of prematurity(ROP). Methods: Seventy-two 7-day-old C57BL/6J mice were divided into two groups. Thirty-six mice in hyperoxic group were exposed to 75% oxygen for 5 days and then to room air for another 5 days. Thirty-six mice in normoxic control were exposed to room air for 10 days. The proliferative neovascular response was estimated by observing the vascular pattern in adenosine diphosphate-ase(ADPase) stained retina flat-mounts and quantitated by counting the number of new vascular cell nuclei extending into the internal limiting membrane in cross-sections. Results: Histology in ADPase stained retina flat-mounts delineated the entire vascular pattern. Hyperoxia-induced neovascularization occurred at the junction between the vascularized and avascular retina in the mid-periphery in all mice exposed to hyperoxia. After 5 days of exposure to hyperoxia at postnatal day 12(P12), the larger central radial vessels became tortuous and constricted and central perfusion became obviously decreased. After return to room air for 2 days at P14, neovascularization was seen. This response was maximal at P17. There was a mean of 43.5 3.6 neovascular nuclei per cross-section extending into the vitreous in hyperoxia compared to 1.3 0.3 nuclei in the normoxia control(P<0.0001). No difference between the right and left eyes was found(P=0.63). Conclusions: Thisanimal model of OIR is reproducible. Because of its quantifiable characteristic, it is useful for the study of pathogenesis of retinal neovascularization and theraputic intervention for ROP.