The hypothermia mimetic synthetic molecule Zr17-2 prevents retinal damage caused by perinatal asphyxia in the rat.

RONAN NAKAMURA 1, MANUEL REY-FUNES 1, JUAN CARLOS FERNÁNDEZ1 , RAFAEL PELÁEZ 2, MANUEL SOLIÑO 1, DANIELA CONTARTESE; CCÉSAR F LOIDL

Mar del Plata

Congreso; LXViI Reunión Científica Anual. Sociedad Argentina de Investigación Clínica (SAIC); 2022

Introduction. Perinatal asphyxia (PA) is responsible for a large proportionof neonatal deaths and numerous neurological sequelae,including visual dysfunction and blindness. During PA, the retina is exposed to ischemia/reoxygenation, which results in neuronalcell death and aberrant angiogenesis and gliosis. Since we havepreviously demonstrated that hypothermia prevents retinal damagecaused by PA. We hypothesized that small molecule mimetics of hypothermiamay also prevent PA-induced retinal degeneration. Materialsand methods. Male rat pups were subjected to an experimentalmodel of PA. Four groups were studied: i) normally delivered (CTL);ii) normally delivered treated with 330 nmols/L zr17-2 (CTL-ZR); iii)exposed to PA for 20 min at 37ºC (PA); and iv) exposed to PA and,then, treated with zr17-2 (PA-ZR). Five days after birth, some ratswere sacrificed and the eyes were studied by TUNEL assay. Fortyfive days after birth, other animals were subjected to electroretinography(ERG), sacrificed, and the eyes studied by histology. Results.Electroretinography showed that PA animals had significant defectsin the a- and b-waves and oscillatory potentials. The same animalspresented a significant increase in the thickness of the inner retinaand a large number of TUNEL-positive cells. All these physiologicaland morphological parameters were significantly prevented by thetreatment with zr17-2. Conclusions. zr17-2 protects from cell deathand restores electrophysiological function in the retina. This moleculecould be used as a treatment to prevent the deleterious visualconsequences of PA.