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A. L. Georgiou, L. Guo, M. F. Cordeiro, T. E. Salt; Assessment of Central Synaptic Transmission in Rats Following RGC Apoptosis Induced by Intravitreal Amyloid-beta (Aβ1-42) Oligomers. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3855.
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Amyloid-beta (Aβ) is elevated in the retinal ganglion cell (RGC) layer of the retina in experimental glaucoma and has been implicated in RGC apoptosis in the disease. Previous studies in our lab have shown that intravitreal injection of Aβ1-42 oligomers induces RGC apoptosis up to 72hrs after injection (Guo et al 2007). This RGC death may have an effect on neurotransmission from RGCs to the superior colliculus (SC). We used the sensitivity of transmission to activation of presynaptic mGluR4 as an indicator of effects on terminals of optic nerve fibres terminating in SC.
Intravitreal injections of Aβ1-42 oligomers (0.55nmol) were given into one eye only (N=9) of Dark Agouti rats. We also looked at a group of age matched untreated control animals (N=10). 16 weeks after injection animals were anaesthetised (Ketamine and Dormitor) and brains were removed for preparation of 400µm parasagital SC slices. Recordings of field excitatory post synaptic potentials (fEPSPs) were made in vitro in the superficial grey layer of the SC in response to optic tract stimulation (Lacey et al 2005). Stimulation was a paired pulse (0.1ms pulses, 20ms separation) repeated at 20sec intervals.
The mGluR4 (Group III) agonist L-AP4 (10µM, bath application) significantly reduced fEPSP amplitudes and reduced paired-pulse depression in all groups of slices. These effects were the same in left (L) or right (R) SC slices in age matched control animals (L 27±3%, N=13, R 31±3%, N=15, P=0.614). However in the animals injected with Aβ1-42 oligomers there was a significantly (P=0.031) larger reduction of the fEPSP due to L-AP4 application in slices receiving input from the injected eye (29±2%, N=16) compared to those receiving input from the uninjected eye (20±1%, N=18).
The larger reduction of the fEPSP due to L-AP4 in slices receiving input from the Aβ1-42 oligomer injected eye may reflect changes in optic nerve terminal function following loss of, or disruption of function, of RGCs. These findings are similar to those that we have seen in the ocular hypertension glaucoma model. These results suggest that there are changes in central synaptic transmission from the RGCs to the SC following RGC apoptosis.
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