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Olachi J. Mezu-Ndubuisi, Justin M. Wanek, Pang-yu Teng,, Felix Y. Chau, Narsa M. Reddy, Amy Lin, Norman P. Blair, Sekhar P. Reddy, Mahnaz Shahidi; Retinal Vascular Oxygen Tension Imaging and Fluorescein Angiography in a Mouse Model of Retinopathy of Prematurity. Invest. Ophthalmol. Vis. Sci. 2012;53(14):4689. doi: https://doi.org/.
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Following premature birth, newborn infants are exposed to the relative hyperoxia of extrauterine conditions compared to the hypoxic in utero condition. This hyperoxic condition is further exacerbated by the use of oxygen to ventilate their lungs due to hypoxemia and decreased compliance from surfactant deficiency. Since excess oxygen contributes to retinopathy of prematurity (ROP), knowledge of retinal oxygenation is needed to determine the balance of the benefit of adequate oxygen delivery with the risk of tissue damage. The purpose of the current study is to report, for the first time, combined in vivo imaging of the retinal vasculature and measurements of vascular oxygen tension in a neonatal mouse oxygen-induced retinopathy (OIR) model of ROP.
Neonatal C57BL/6J mice at post-natal day 7 (P7) were either exposed to 75% oxygen (N = 2) or room air control (N = 3) for 5 days, then both groups were exposed to room air for an additional 5 days. On P17, in vivo phosphorescence lifetime imaging and fluorescein angiography (FA) were performed on anesthetized mice pups to measure retinal vascular oxygen tension and visualize retinal vasculature, respectively. Retinal histology was also performed on both control and OIR mice.
In the control mice, FA revealed perfusion of all retinal blood vessels and a uniform capillary network. In the OIR mice, relatively large retinal regions displayed severe capillary non-perfusion. These regions were within 3 disc diameters from the optic nerve head edge. Resembling features of severe human ROP, tortuous major vessels were seen on FA while dilation of retinal arteries and veins, and neovascularization were observed on both FA and retinal histology. In the control mice, retinal arterial and venous oxygen tension measurements were 28 ± 5 mmHg and 22 ± 5 mmHg, respectively. In the OIR mice, retinal arterial and venous oxygen tension measurements were 21 ± 12 mmHg and 12 ± 12 mmHg, respectively. The arterio-venous oxygen tension differences in control and OIR mice were 5 ± 1 mm Hg and 9 ± 0.1 mmHg, respectively.
Combined in vivo retinal vasculature and oxygen tension imaging holds promise for investigating retinal vascularization and oxygenation abnormalities in experimental OIR. It has potential for testing therapeutic interventions which can be translated clinically to prevent or treat ROP.
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