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A. Whitlock, K. Corcoran, D. S. Rice; The PERG as a Useful Tool in Demonstrating Functional Neuroprotection in the Mouse. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5304.
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Numerous glaucomatous retinal degeneration models have been developed using the mouse as the model organism. These models have been very valuable in identifying potential new therapies for the treatment of glaucoma. The endpoint used to define neuroprotection for most of these studies is histological counting of cells in the retinal ganglion cell (RGC) layer. Limitations to using histology as the defining endpoint are: 1) it is terminal and 2) it often requires using large numbers of animals when performing longitudinal studies. The purpose of this study was to establish the relationship between histology of the inner retina and pattern electroretinogram responses (PERG) in the NMDA-induced excitotoxicity model in mice in order to determine whether or not PERG measurements can be used as a substitute for histological examination of the retina.
Wild-type C57BL/6 mice were subjected to an NMDA-induced excitotoxicity challenge in the presence and absence of the glutamate receptor antagonist, MK-801. One week following intravitreal injection of either PBS, 5 mM NMDA, or 5 mM NMDA + 100 µM MK-801, inner retinal function was assessed by PERG analysis, followed by histological analysis of the RGC layer. Damage was quantified by counting cells within a 500 µm area on either side of the optic nerve head.
Intravitreal injection of NMDA resulted in a significant decrease in PERG amplitudes (9.95 ± 1.5 µV; p<0.001, n=15) and a significant decrease in cell number (35.00 ± 3.69 cells/500 µm; p<0.001, n=9) when compared to PBS injected eyes. Co-injection of MK-801 with NMDA resulted in significant improvement in PERG amplitude (p< 0.01, n=11) and corresponded with a significant increase (p< 0.05, n=9) in the number of cells in the RGC layer when compared to NMDA alone.
A correlation between cell number in the RGC layer and inner retinal function was observed in an NMDA-induced excitotoxicity challenge. This finding indicates that PERG analysis is a potentially valuable tool for understanding the physiological outcomes of neuroprotective strategies in glaucoma and has the added benefit of reducing the number of animals required for these studies.
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