Variability in the Electroretinographic Response of Laboratory Animals

Abstract

Purpose : To compare variability of the dark-adapted electroretinogram (ERG) in large samples sizes of commonly used species of laboratory animals.

Methods : All ERGs were collected from normal eyes, naïve to any treatment or surgical intervention. Species tested included monkeys (cynomolgus, N=160), dogs (beagle, N=142), minipigs (Yucatan, N=40), pigmented rabbits (Dutch belted, N=349), albino rabbits (New Zealand white, N=411), albino rats (Sprague Dawley, N=84), and mice (C57/BL6, N=72). All animals were dark-adapted for at least 2 h, anesthetized, and had their pupils dilated prior to testing. ERGs were recorded in response to 2.5 cd-s m^-2 flashes, delivered in a large ganzfeld dome. ERGs were digitally filtered, and B-wave amplitudes computed automatically. B-wave amplitudes from othe right eye from each animal were entered into the analyses.

Results : The distribution of B-wave amplitudes were mildy skewed in all specied tested. The fit to a normal distribution was improved by a log or square-root transformation. Coefficients of variation (COV) for B-amplitudes awere generally similar across species. The log B-wave amplitude COV for the cynomolgus monkey (0.04), was similar to the beagle dog (0.05), the albino rat (0.06), followed by the minipig andpigmented rabbit (both 0.60). The C57/BL6 mouse COV was modestly higher (0.11).

Conclusions : Nonclinical safety and efficacy studies of ocular drugs and devices frequently use ERG to non-invasively assess the functional status of the retina. There is little published data on the statistical properties of ERG responses of laboratory animals that are based on sufficiently large sample sizes. Here we show that variability in ERG amplitudes as a proportion of the mean is similar across commonly used laboratory species and similar to the reported DA B-wave COV in humans (0.05). The data presented here can be used to inform study design to adequately power studies and to facilitate interpretation and comparison of ERG results both within and between laboratory species.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.