Quantification of Ischemic Damage in the Rat Retina: A Comparative Study Using Evoked Potentials, Electroretinography, and Histology

Abstract

To identify objective criteria to quantify visual function in the rat for developing therapeutic strategies to protect neuronal cells after ischemia. The impact of ocular ischemia on luminance and frequency-modulated contrast vision was compared with the function of outer retinal cells and the number of intact retinal ganglion cells (RGCs). Ischemia was induced in Brown-Norway rats by elevating the intraocular pressure to 120 mm Hg for 30, 45, 60, and 90 minutes. Visual function was evaluated by visual evoked potentials (VEPs) in awake, freely moving rats. Retinal function was analyzed with scotopic and photopic electroretinography (ERG). RGCs were quantified in retinal flatmounts after postischemic injection of tracer into the superior colliculus. The response to flicker stimulation in VEP recordings decreased as the ischemic episodes increased. The susceptibility to ischemic damage was more pronounced when potentials were evoked with stimuli at higher frequencies. In ERG recordings, ischemia reduced oscillatory potentials and photopic flicker responses more intensely than scotopic a- and b-waves. In counting the RGCs, the reduced cell density correlated significantly with all electrophysiological parameters. The duration of ischemia with half-maximal inhibitory effect was between 36 and 58 minutes for VEPs and between 36 and 41 minutes for ERG, and it was 51 minutes for RGCs. The amounts of reduction in VEPs, ERG, and RGCs differed as the duration of ischemia increased. The electrophysiological parameters presented in this study may serve as a useful addition to morphologic evaluations in future neuroprotection studies in vivo.