Changes in NMDA receptor contribution to synaptic transmission in the brain in a rat model of glaucoma.
In the age-related, blinding disease glaucoma, retinal ganglion cells (RGCs) degenerate, possibly affecting glutamatergic retinofugal transmission to the brain. The superior colliculus (SC) is a major central target of retinofugal axons in the rodent, a much used disease model. We investigated the contribution of NMDA-type glutamate receptors to retinocollicular transmission in a rat glaucoma model, using a SC brain slice preparation to determine the sensitivity of synaptic responses to the NMDAR antagonist D-AP5. At 32weeks after induction of experimental glaucoma, but not earlier, there was an increase in NMDAR contribution to SC synaptic responses in slices receiving input from glaucomatous eyes. This suggests that there are changes in NMDAR function after RGC degeneration in experimental glaucoma, which may represent functional SC compensation through plasticity via NMDARs. This has implications for studies carried out using rodent glaucoma models, especially those evaluating potential treatment strategies, as it suggests that functional changes in the central visual system need to be considered in addition to those in the eye. Furthermore, the data underline the need for early therapeutic intervention in order to pre-empt subsequent central functional changes.
Georgiou
A L
AL
Department of Visual Neuroscience, UCL Institute of Ophthalmology, London, UK.
Guo
L
L
Cordeiro
M F
MF
Salt
T E
TE
D000704:Analysis of Variance; D000818:Animals; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005901:Glaucoma / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000502:physiology*; D013477:Superior Colliculi / Q000378:metabolism / Q000503:physiopathology*; D013569:Synapses / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology*; D014795:Visual Pathways / Q000378:metabolism / Q000503:physiopathology*
D016194:Receptors, N-Methyl-D-Aspartate
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