Abstract
Abstract: :
Purpose: Rodents have emerged as economical and useful animal models for studying neuroprotective strategies against retinal ganglion cell (RGC) death. The scotopic threshold response (STR) of the dark-adapted electroretinogram (ERG) of rats could be potentially useful for monitoring the physiological activity of RGCs in vivo. The purpose of this study was to determine whether the STR of the rat reflects the activity of inner-retinal neurons as previously shown in mice, cats and monkeys. Methods: Dark-adapted ERGs were recorded differentially between DTL fiber electrodes from anesthetized (ketamine, 60 mg/kg/hr, xylazine 6 mg/kg/hr) Harlan Sprague-Dawley rats before and after intravitreal injection of tetrodotoxin (TTX, 2.5 micro liters of 4-40 micro molar concentration) or N-Methyl-D-Aspartic acid (NMDA, 2.5 micro liters of 4-40 mM concentration) to suppress inner-retinal activity. The pupils were dilated with phenylephrine hydrochloride (2.5%) and accommodation was blocked with atropine sulfate (1%). An Espion system (Diagnosys, MA) was used for stimulus presentation and data acquisition. The stimuli consisted of brief (<4ms) full field blue LED flashes of intensities ranging between -3.5 and 2 log scot td.s. Results: The control ERG responses at lower intensities (around -3.35 log scot td.s) consisted of a prominent negative potential, the negative STR (nSTR) that had maximal amplitude around 250ms. At higher flash intensities, a positive potential (with peak time around 140ms) could be seen emerging from the leading edge of the nSTR. As flash intensity increased from -3.24 to -2.54 log scot td.s the amplitude as well as the peak time of this positive potential increased. With further increase in flash intensity the positive potential resembled the standard b-wave with its time to peak decreasing to about 70ms around -0.55 log scot td.s. Typical a-wave was seen at higher flash intensities. Following intravitreal injection of TTX or NMDA, nSTR was completely eliminated. Responses at higher flash intensities (-3.24 log scot td.s.) mainly consisted of a positive potential that unlike the control responses at these intensities had time to peak around 185ms that continuously decreased as flash intensity was increased. No significant changes were observed with the a-wave. Conclusions: The nSTR of the rat reflect the combined electrical activity of inner-retinal neurons as previously shown in other species. The positive potential on the leading edge of the nSTR likely represents the positive STR (pSTR) that also reflects reflects inner retinal activity as shown in other species. The STR could be potentially useful in monitoring inner-retinal activity in rats.
Keywords: electroretinography: non-clinical • ganglion cells • animal model