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Pedro de la Villa, Estella Calvo, Laura Ramirez, Francisco Germain, Violeta Gomez-Vicente, Nicolas Cuenca; Damage of Inner Retinal Cells Induced by Neurotoxic Effect of Glutamate Receptor Agonists. Invest. Ophthalmol. Vis. Sci. 2013;54(15):726.
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Animal models of retinal ganglion cell degeneration have been widely proposed. Glutamate agonists such as kainic acid (KA) or N-methyl-D-aspartic acid (NMDA) have been used for selective ganglion cell damage in the past years. However, no clear information about the effect of these neurotoxic agents on other retinal cells have been shown to date. Our work tries to address the neurotoxic effect of KA and NMDA on inner retinal cells and retinal functionality.
Retinal neurotoxicity was induced in right eyes of C57BL6 mice by intraocular injection of 1 μl of PBS containing increased concentrations of KA and NMDA. Left eyes injected with 1 μl of just PBS were used as controls. Retinal functionality was addressed by binocular electroretinogram recordings (ERG) form control and damaged eyes one week after intraocular injection. Surviving ganglion cells were estimated by cell counts of Brn3a immunolabeling on flat mount retinas one week after eye injections. Immunoreactivity for horizontal, bipolar, amacrine and ganglion cells was also performed on retinal sections from control and damaged eyes.
We show that injection of increased concentrations of KA induces selective death of retinal ganglion cells. Similar effect was observed when NMDA was intraocularly injected at increased concentration. ERG recordings form NMDA or KA injected animals showed clear signs of ganglion cell loss. When NMDA and KA were injected together, an abrupt disruption of the b-wave ERG was observed, thus indicating the damage of inner retinal cells. Moreover, specific retinal cell labeling on retinal trasverse sections from damaged eyes shows a clear disruption of the inner retina, that affects not only to ganglion cells but also to all inner retinal cells.
The present work shows that NMDA and KA glutamate receptor agonists, are able to induce a severe damage of the inner retinal cells when injected together into the eyeball.
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