The Pattern Electroretinogram as a Tool to Monitor Progressive Retinal Ganglion Cell Dysfunction in the DBA/2J Mouse Model of Glaucoma

Abstract

To determine the baseline characteristics, reliability, and dynamic range of the pattern electroretinogram (PERG) as a tool to monitor progressive RGC dysfunction in the DBA/2J mouse model of glaucoma with spontaneously elevated intraocular pressure (IOP). PERGs were recorded from 56 undilated eyes of 28 anesthetized (ketamine-xylazine-acepromazine) DBA/2J mice of different ages (2-4 months, n = 44 eyes; 12-14 months, n = 12 eyes) in response to contrast reversal of gratings that maximize PERG amplitude (95% contrast, 1-Hz reversal, 0.05 cyc/deg spatial frequency, 50 degrees x 56 degrees field size). Robust averaging (1800 sweeps) was used to isolate PERG from background noise. Cone-driven ERGs in response to diffuse light flashes superimposed on a rod-adapting background (FERG) were also recorded. PERGs had consistent waveforms and were reproducible across batches of mice and operators. In 2- to 4-month-old mice (prehypertensive stage), the PERG amplitude (mean, 8.15 +/- 0.4 microV [SEM]) was considerably larger than the noise (mean 1.18 +/- 0.1 microV). The test-retest variability (two different sessions 1 week apart) and interocular asymmetry of PERG amplitude was approximately 30%, and that of PERG latency was approximately 17%. In 12- to 14-month-old mice (advanced hypertensive stage) the PERG amplitude (mean, 1.29 +/- 0.12 microV) was close to that of noise. In 12- to 14-month-old mice the FERG was reduced to a lesser extent compared with the PERG. The PERG has an adequate signal-to-noise ratio, reproducibility, and dynamic range to monitor the progression of functional changes in the inner retina in DBA/2J mice.