Role of hypoxia during normal retinal vessel development and in experimental retinopathy of prematurity

Abstract

Purpose: To test the hypothesis that retinal hypoxia is present during vascular development in normal rat pups and in a newborn rat model of retinopathy of prematurity (ROP).

Methods: Preretinal vitreous PO(2) measurements were made during room air breathing using (19)F magnetic resonance spectroscopy (MRS) and a perfluoro-15-crown-5-ether droplet in normal adult and newborn (postnatal day [P]1-P20) rats, and in newborn rats exposed first to 14 days of variable oxygen (before NV) and six additional days in room air after variable oxygen exposure (during NV). After each experiment, blood gas values were measured, and retinas were isolated. Retinas were adenosine diphosphatase (ADPase) stained, and flatmounted to determine peripheral avascular extent and NV incidence and severity.

Results: In the vascularized rat retina, no significant difference (P > 0.05) was found between the droplet-derived preretinal vitreous oxygen tension (24 +/- 2 mm Hg, mean +/- SEM, n = 18) and previously reported electrode-measured oxygen tension (22 +/- 1 mm Hg). Only during normal retinal vessel growth (P1-P10) and before the appearance of NV was evidence for retinal hypoxia found at the border of the vascular and avascular retina. However, the mean PO(2) (range, 24-28 mm Hg) over the vascular retina was not different (P > 0.05) between any of the newborn rat groups in this study.

Conclusions: (19)F MRS of a perfluorocarbon droplet provides an accurate measure of preretinal vitreous oxygen tension in rats. These data support an important role of physiologic hypoxia in normal retinal circulatory development and raises the possibility that, in experimental ROP, retinal hypoxia is a necessary but not sufficient condition for the development of retinal NV.