Retinal neuroprotection against ischemia/reperfusion damage induced by global and local hypothermia

SALIDO, E; DORFMAN, D; CHIANELLI, MS; ROSENSTEIN, RE

San Diego, California

Congreso; Society for Neuroscience Annual Meeting 2013; 2013

Society for Neuroscience

Purpose: Retinal ischemia could provoke blindness. There is no effective treatment against retinal ischemic damage. We investigated whether a brief global or local hypothermia could induce ischemic tolerance in the rat retina. Methods: Ischemia was induced in male Wistar rats by increasing intraocular pressure to 140 mm Hg for 50 minutes. One day before ischemia, animals underwent a 20-minute period of hypothermia by lowering the whole body temperature to 32ºC or by cooling only one eye to 25ºC for 30 min. Two weeks after ischemia, animals were subjected to electroretinography (ERG) and histological analysis. Moreover, glutamate uptake was assessed using 3H-glutamate, and glutamine synthetase activity was assessed by a spectrophotometric assay. Results: Retinal ischemia induced a significant decrease in oscillatory potentials, and scotopic ERG a- and b-wave amplitude, which was significantly prevented by global or monocular hypothermia. Retinal ischemia induced a significant decrease in glutamate uptake and glutamine synthetase activity, whereas monocular hypothermia prevented the effect of ischemia on glutamate recycling. The intravitreal injection of supraphysiological concentrations of glutamate mimicked electroretinographic and histological alterations provoked by ischemia, which were significantly abrogated by hypothermic preconditioning. Conclusions: These results indicate that hypothermia significantly protected retinal function and histology against ischemia/reperfusion injury. Hypothermic preconditioning could provide a relatively low-risk approach for treating retinal ischemic pathologies.