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A. L. Georgiou, L. Guo, M. F. Cordeiro, T. E. Salt; Assessment of Central Synaptic Transmission in Experimental Glaucoma and Its Treatment in Rats. Invest. Ophthalmol. Vis. Sci. 2007;48(13):207.
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© ARVO (1962-2015); The Authors (2016-present)
Retinal ganglion cell (RGC) degeneration in glaucoma may have effects on synaptic function in central target areas. Amyloid-ßετα (Aß) is elevated in the RGC layer of the retina in experimental glaucoma. This study was carried out to assess the effect of experimental glaucoma and a treatment strategy using an Aß antibody on neurotransmission from RGCs to the superior colliculus (SC). We used paired pulse ratio (PPR) and sensitivity of transmission to activation of presynaptic mGluR4 as indicators of effects on terminals of optic nerve fibres terminating in SC.
Chronic ocular hypertension (OHT) was induced in rats using the Morrison method in one eye and treated eyes were injected intravitreally with either vehicle (N=4) or an Aß1-20 antibody (BioSource International) (N=5). We also looked at a group of age matched untreated control animals (N=5). 16 weeks after surgery animals were anaesthetised (Ketamine and Dormitor) and brains were removed for preparation of 400um 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. Stimulation was a paired pulse (0.1ms pulses, 20ms separation) repeated at 20sec intervals.
There was no significant difference in the PPR between SC slices in any of the groups of rats. The mGluR4 (Group III) agonist L-AP4 (10uM) significantly reduced fEPSP amplitudes in all groups of slices. These effects were the same in left or right SC slices in control animals (26 ± 5% reduction, N=8, 31 ± 4%, N=8, respectively, P=0.45). Similarly, the effect of L-AP4 was the same in slices receiving input from the untreated eye compared to slices receiving input from the OHT and vehicle treated eye (19 ± 6%, N=6, 22 ± 5%, N=7, P=0.64). However slices receiving input from the OHT and Aß antibody treated eye showed a significantly (P=0.04) larger fEPSP reduction due to L-AP4 addition (39 ± 10%, N=8) compared to the contralateral slices (14 ± 4%, N=9).
The presynaptic effect of L-AP4 on fEPSPs was similar in SC slices with input from the untreated eye or slices with input from OHT/vehicle treated eyes and control animals. This suggests that there may be some central compensation for RGC degeneration in these animals. The greater effect of L-AP4 in slices receiving input from the OHT/Aß antibody treated eye may reflect plastic changes in optic nerve terminal function following changes in RGC function due to reduction of Aß levels.
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