Changes in the modulation of retinocollicular transmission through group III mGluRs long after an increase in intraocular pressure in a rat model of glaucoma

Abstract

AbstractMetabotropic glutamate receptors (mGluRs) have been shown to be involved in the modulation of retinocollicular neurotransmission. In glaucoma, retinal ganglion cells (RGCs) degenerate, which may have an implication on this transmission as the superior colliculus is their major central target in the much-used rodent models of the disease. We have investigated this using anin vitroslice preparation of the superior colliculus by eliciting field excitatory postsynaptic potentials (fEPSPs) through optic tract stimulation in a rat ocular hypertension model of glaucoma. Application of the group III mGluR agonist L-AP4 reduced the peak amplitude of the fEPSP in superior colliculus slices through presynaptic mechanisms as previously shown in our lab. At 3 and 16 weeks after surgery, there were no significant differences in the effect of L-AP4 on fEPSP peak amplitude in the superior colliculus slices receiving input from the glaucomatous eyes [elevated intraocular pressure (IOP)] compared to those with input from the unoperated eyes (normal IOP). However, at 32 weeks, the fEPSP peak amplitude was reduced to a significantly greater degree during L-AP4 application in the elevated IOP slices compared to normal IOP slices. At all time points, there were no significant changes in the baseline amplitudes of fEPSPs or the stimulus intensities required to evoke fEPSPs. These results suggest that the modulation of synaptic transmission through group III mGluRs on RGC terminals to the superior colliculus is changed at later stages due to RGC degeneration through IOP elevation. These changes may be compensatory changes possibly through plasticity in the RGC terminals of surviving cells, which may be due to increases in the numbers of group III mGluRs. This result may have implications on further treatment studies carried out using these models of glaucoma as changes in the central visual system may need to be considered along with the retinal changes that occur.