Expression of antioxidant protective proteins in the rat retina during prenatal and postnatal development

PURPOSE. In retinopathy of prematurity, capillary growth in the retina is a ttentuated. Subsequent cyclic elevation of oxygen levels leads to renewed c apillary growth that may eventually result in retinal detachment, It is hyp othesized that the sensitivity of the premature retina to oxidative shock r esults from the absence of antioxidant protective proteins. METHODS. The expression of heme oxygenase-1, metallothionein, superoxide di smutase, and catalase mRNAs was measured in retinas of rats from 6 days bef ore birth to 4 days after birth using in situ hybridization and semiquantit ative reverse transcription-polymerase chain reaction with Southern blot an alysis. RESULTS. Superoxide dismutase mRNA was expressed to a similar extent at all time points. Metallothionein mRNA expression, which was high at embryonic days (E) 16 and 18, decreased to low levels by the time of birth and remain ed low at least until 4 days after birth. Catalase mRNA expression was low until birth and increased until at least postnatal day 4. Heme oxygenase-1 mRNA showed low expression at E16 and E18, increased before birth, and then diminished. CONCLUSIONS. Four antioxidant protein mRNAs showed very different patterns of expression in the rat retina, Two of these proteins, heme oxygenase-l an d catalase, were expressed at relatively low levels until approximately the rime of birth. The former is important in protection against heme-mediated generation of reactive oxygen species, whereas the latter protects against hydrogen peroxide-generated damage. As a result of the low expression of t hese mRNAs, and presumably the proteins encoded by them, the premature rat (and probably the premature human) is likely to be born without a full comp lement of antioxidant defenses.