An increase in superoxide dismutase ameliorates oxygen-induced retinopathy in transgenic mice

Oxygen therapy is a well-recognized risk factor for retinopathy of prematurity. We examined whether an increase in the naturally occurring enzyme copper-zinc superoxide dismutase (CuZnSOD), which controls oxygen, can reduce the severity of oxygen-induced retinopathy in a mouse model.

Seven transgenic mice overexpressing CuZnSOD and six wild-type mice were exposed to 75% oxygen from postnatal day 7 to 12. Seven transgenic mice and five mice of the wild type were kept in room air and served as controls. Fluorescein-conjugated dextran angiography of retinal vasculature was performed and flat-mounted preparations were evaluated by scoring blood vessel growth, blood vessel tuft formation, extraretinal neovascularization, degree of central constriction, and tortuosity of vessels. In addition, quantification of the number of blood vessel tufts was performed in a masked fashion with haematoxylin and eosin staining of paraffin-embedded eye sections.

The mean retinal score+/-SD obtained by the wild-type mice was 9.4+/-2.0, whereas the transgenic mice overexpressing CuZnSOD obtained a value of 2.4+/-1.6 (P=0). The two control groups (wild type and transgenic) that were kept in room air, each obtained a score of 0. Significantly fewer extraretinal vascular tufts were seen in the transgenic mice (0.26+/-0.34) than in the wild-type mice (4.27+/-1.6) after both groups were exposed to oxygen (P<0.001).

The results suggest that high SOD activity protects neonatal mice against oxygen-induced retinopathy, and support the assumption that oxygen radicals are a major causative factor in oxygen-induced retinopathy.