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Alfredo Martinez, Manuel Rey-Funes, Ignacio Larrayoz, Daniela S Contartese, Verónica B Dorfman, Federico Rolón, Anibal Sarotto, César F Loidl; Hypothermia protects from perinatal asphyxia-induced retinopathy, when applied either during or after asphyxia. Invest. Ophthalmol. Vis. Sci. 2016;57(12):4597.
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© ARVO (1962-2015); The Authors (2016-present)
Perinatal asphyxia (PA) occurs in 2-4 cases per 1,000 births and 30% of affected neonates die as a result. Among the survivors, 50% present neurological sequelae, including retinopathy. We have previously shown that hypothermia during PA can prevent all manifestations of PA-induced retinopathy. Here we investigate whether hypothermia given after the asphyctic event is also effective.
Pregnant Sprague-Dawley rats were sacrificed after vaginal delivery of their first pup. Full-term fetuses, still inside the uterus, were subjected to asphyxia performed by transient immersion in a water bath for 20 minutes at either 37°C (PA group) or at 15°C (HYP group). After this, pups were given to surrogate mothers. Half of the asphyctic neonates were subjected to hypothermia at 8°C for 15 min (HYP-PA group). Pups delivered by normal birth were used as controls (CTL group). Young rats were sacrificed at different times and eyes were processed for RNA and protein extraction or for morphological studies.
Animals in the PA group had a significant thickening of the inner retina compared to the CTL group (p<0.05) due to vascular and glial hypertrophy. These changes were not observed in either of the groups subjected to hypothermia. The protective mechanism was not mediated by HIF-1α since its expression was increased in all animals subjected to PA (p<0.05) independently of cold exposure. Cold-shock proteins could mediate cold-induced cellular effects. We studied expression of RNA-binding motif protein 3 (RBM3) and cold inducible RNA-binding protein (CIRP) in our model by qRT-PCR, Western blotting, and immunofluorescence (Fig. 1). Both proteins increased their expression in animals subjected to hypothermia (p<0.05) while they were low in CTL and PA groups.
Hypothermia prevents PA-induced retinopathy when given either during or after the asphyctic event. This effect seems to be mediated by overexpression of cold-shock proteins. Deeper molecular studies will help in better understanding the specific mechanisms of this protective intervention.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
Figure 1. Confocal microscopy images of the 4 experimental groups (CTL, PA, HYP, and HYP-PA) stained with antibodies against CIRBP (red, first column) and RBM3 (green, second column). The third column is a combination of the previous ones to show colocalization. Bar= 20 µm.
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