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Markus Tschopp, Rahel Zulliger, Sebastian Wolf, Volker Enzmann; Electroretinogram for the Analysis of Pharmacologically Induced Retinal Degeneration in the Mouse. Invest. Ophthalmol. Vis. Sci. 2011;52(14):709.
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To study retinal degeneration in the mouse we employed sodium iodate (NaIO3), which selectively destroys RPE cells and N-methyl-N-nitrosourea (MNU), which induces photoreceptor cell death. The aim of this study was to analyze retinal damage with the electroretinogram (ERG), which allows to identify the retinal cell type responsible for the deficit and to quantify the changes.
Male C57BL/6 mice were treated with single i.v. injection of NaIO3 (15, 25 mg/kg) or i.p. injection of MNU (30, 60 mg/kg). ERG was measured at different time points post injection. For this, the overnight dark adapted animals were anesthetized, their pupils dilated, and placed on a specially designed, heated mouse table. ERG responses were recorded simultaneously from both eyes by means of gold wire electrodes positioned to touch the cornea. Gold wires were also positioned in the mouth as reference electrodes. Standardized flashes of light with different intensities [-25, -20, -10, 0 dB (3 cd/m2/s)] were presented to the mouse in a Ganzfeld bowl. After recording the rod-isolated responses c-wave measurement was performed. Animals were then light adapted for 10 minutes to record cone-isolated responses (0 dB). To correlate the ERG results to the underlying degeneration, enucleated eyes were paraffin embedded and sections at the optic nerve head were H&E stained for morphometric measurements of the outer nuclear layer (ONL).
Injection of 15 mg/kg NaIO3 induced only minor reduction of all wave forms, which were thereafter stable over time. 25 mg/kg NaIO3 treatment was followed by an augmented b-wave one day after injection. Beginning after three days all wave forms were significantly reduced over time. ERG data correlated with morphometric data, where concentration and time dependent reduction of ONL was found. Likewise, 30 mg/kg MNU reduced the electroretinogram only modest. In contrast, 60 mg/kg MNU led to an almost complete extinction of the ERG already one day after injection. Again, the ERG data correlated with morphometric data, where significant reduction of ONL was found.
Modified clinical ERG setup allowed us to measure the rod and cone response, the response of the retinal pigment epithelium, the oscillatory potentials, and the flicker response in animals with retinal damage. Both, the NaIO3 and the MNU model, showed a time and concentration dependent reduction of the ERG.
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