Hypothermia applied during or after perinatal asphyxia prevents retinal damage in rats

MANUEL REY-FUNES1, DANIELA S. CONTARTESE1, MANUEL SOLIÑO1, JUAN CARLOS FERNÁNDEZ1, RAFAEL PELÁEZ2, JUAN JOSÉ LÓPEZ-COSTA1, IGNACIO M. LARRÁYOZ2, VERÓNICA B. DORFMAN3, ; ALFREDO MARTINEZ; LAURA SCÉVOLA, JULIA TEITELBAUM, SILVIA ODDO, ESTELA CENTURIÓN, CÉSAR FABIÁN LOIDL, SILVIA KOCHEN, LUCIANA D´ALESSIO

Murcia

Congreso; XX CONGRESO DE LA SOCIEDAD ESPAÑOLA DE HISTOLOGÍA E INGENIERÍA TISULAR (SEHIT); 2019

SOCIEDAD ESPAÑOLA DE HISTOLOGÍA E INGENIERÍA TISULAR (SEHIT),

Introduction. Perinatal asphyxia (PA) can be the cause of different degrees of retinopathy, which in severe cases can lead to blindness. Clinical studies reveal that obstetric complications and in particular PA develop ischemic retinopathy (IR). In a rat model of PA, we have shown neurodegeneration, gliosis, and neurovascularization compatible with IR. In this model, a protective effect of hypothermia was demonstrated when applied during PA. In the present work we want to show that hypothermia has a protective effect both when applied during and immediately after PA. Since CIRP (Cold-inducible RNA-binding protein) and RBM3 (RNA binding motif protein-3) are proteins inducible by cold that could mediate the beneficial effects of hypothermia, we also investigated the molecular response of these proteins in the retina when exposed to cold. Materials and methods. Rats exposed to PA were subjected to hypothermia during or after PA using a well-tested experimental model. In order to evaluate the integrity of the visual pathway, animals were subjected to electroretinography at 60 days of age. Molecular and histological techniques were applied to the eyes of all experimental groups collected at 6, 12, 24 and 48 h, and 6 days after birth.Results. A significant increase in the nucleotide and protein expression of CIRP and RBM3 was observed from 12 h in both controls and asphyctic animals exposed to hypothermia. At 24 h, a significant decrease in the expression of CIRP and RBM3 was observed, by Western blotting, in the animals treated with hypothermia when compared to the PA animals. The expression of CIRP and RBM3 was located in ganglionic neurons and cells of the inner nuclear layer by immunohistochemistry and confocal microscopy. A significant decrease in TUNEL positive cells was observed in the experimental groups treated with hypothermia when compared with the PA groups under normothermia conditions. Furthermore, PA resulted in a significant reduction in the amplitude of the a and b wave and oscillatory potentials of the electroretinograms whereas animals treated with hypothermia had a significant correction of these values. Conclusions. Hypothermia can be used as a useful and affordable method to prevent asphyxia-related vision losses. This work opens new perspectives to understand the cold-inducible molecular mechanisms that may be involved in the neuroprotection triggered by the treatment with a hypothermic shock.