Georgiou Anne L, Guo Li, Cordeiro M Francesca, Salt Thomas E
Department of Visual Neuroscience, UCL Institute of Ophthalmology, London, UK.
Vis Neurosci. 2012 Sep;29(4-5):237-46. doi: 10.1017/S0952523812000193. Epub 2012 May 30.
Metabotropic 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 an in vitro slice 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.
代谢型谷氨酸受体（mGluRs）已被证明参与视网膜-丘脑神经传递的调节。在青光眼患者中，视网膜神经节细胞（RGCs）会退化，这可能会影响这种神经传递，因为在常用的啮齿动物青光眼模型中，上丘是它们的主要中枢靶点。我们通过在大鼠青光眼高眼压模型中，利用上丘的体外脑片制备，通过刺激视束诱发场兴奋性突触后电位（fEPSPs），对此进行了研究。如我们实验室之前所示，应用III组mGluR激动剂L-AP4通过突触前机制降低了上丘脑片fEPSP的峰值幅度。在手术后3周和16周，与从未手术眼（正常眼压）接收输入的上丘脑片相比，L-AP4对从青光眼眼（眼压升高）接收输入的上丘脑片fEPSP峰值幅度的影响没有显著差异。然而，在32周时，与正常眼压脑片相比，在眼压升高的脑片中应用L-AP4期间，fEPSP峰值幅度降低的程度明显更大。在所有时间点，fEPSPs的基线幅度或诱发fEPSPs所需的刺激强度均无显著变化。这些结果表明，由于眼压升高导致RGC退化，在后期通过III组mGluRs对RGC终末到上丘的突触传递调节发生了改变。这些变化可能是通过存活细胞RGC终末的可塑性产生的代偿性变化，这可能是由于III组mGluRs数量增加所致。这一结果可能对使用这些青光眼模型进行的进一步治疗研究有影响，因为在研究中可能需要同时考虑中枢视觉系统的变化以及视网膜发生的变化。
