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Editors Selection IGR 9-4

Electrophysiology: PERG

Comment by Christopher Bowd on:

16970 The pattern electroretinogram as a tool to monitor progressive retinal ganglion cell dysfunction in the DBA/2J mouse model of glaucoma, Porciatti V; Saleh M; Nagaraju M, Investigative Ophthalmology and Visual Science, 2007; 48: 745-751

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Techniques for measuring change in ganglion cell activity over time in animal models of glaucoma are obviously important for investigating newly developed neuroprotective drugs. In a carefully conducted study, Porciatti et al. (143) demonstrate a decrease in (presumed) ganglion cell function in DBA/2J mice (a strain that develops increased IOP and ganglion cell loss with age, likely as a result of pigmentary dispersion) using a simple, but elegant technique (hand-formed electrodes encircling the eye). Using optimized (based on considerable prior research) PERG stimuli, these authors show a large decrease (approximately 98% of dynamic range) in PERG amplitude in older (12-14 months) mice (n = 6) compared to young (2-3 month old) mice (n = 22). A control condition shows a much smaller decrease in flash ERG measurements, suggesting this effect likely is not the result of decreased outer retinal function.

PERG measurements can detect change in ganglion cell activity associated with increased IOP and ganglion cell loss in the DBA/2J mouse

The decrease in PERG activity observed between old and young mice strongly suggests that this technique is promising for detecting change over time but it does not demonstrate it. Although the decreases in PERG amplitude are striking, test-retest variability is quite high (e.g., 30%) and this variability could mask true change. Ideally, longitudinal measurements in the same animals should be obtained to show a steady decrease in PERG activity with increasing age (i.e., increasing IOP and ganglion cell loss). In addition, histological validation of presumed ganglion cell loss is advised. Apparently work by this group addressing both of these issues is well under way (Saleh et al., 2007, ARVO e-abstract 210).

This well-done study is important because it strongly suggests thatPERG measurements can detect change in ganglion cell activity associated with increased IOP and ganglion cell loss in the DBA/2J mouse, an easily obtained and inexpensive animal model of glaucoma.

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