Abstract
Purpose :
Presynaptic modulation of γ-aminobutyric acid (GABA) release by an alpha7 nicotinic acetylcholine receptor (α7-nAChR) agonist promotes retinal ganglion cell (RGC) survival and function, as suggested by a previous study on a chronic glaucomatous model from our laboratory. However, the role of excitatory and inhibitory amino acid receptors and their interaction with α7-nAChR in physiological and glaucomatous events remains unknown.
Methods :
Using patch clamp techniques, the GABA-elicited membrane current and miniature excitatory postsynaptic currents (mEPSCS) of RGCs and the NMDA-gated current (INMDA) were detected in rat retinal slices. The expression of the GABAA receptor and NMDA receptors (NMDAR) subunit NR1, NR2A and NR2B in retinas were detected using western blotting and immunostaining.
Results :
Whole-cell patch-clamp recordings from RGCs revealed profound changes in the GABAA receptor and NMDAR properties under glaucoma conditions. The α7-nAChR specific agonist PNU-282987 enhanced the amplitude of currents elicited by GABA and reduced the amplitude of currents elicited by NMDA. Pretreatment with the α7-nAChR antagonist methyllycaconitine (MLA) blocked the PNU-282987-induced positive modulation of the GABAA receptor and the negative modulation of the NMDAR. The frequency and the amplitude of glutamate receptor-mediated miniature glutamatergic excitatory postsynaptic currents (mEPSCs) were not significantly different between the control and glaucomatous RGCs. Additionally, PNU-282987–treated slices showed no alteration in the frequency or amplitude of mEPSCs relative to control RGCs. Moreover, we showed that expression of the α1 subunit of the GABAA receptor was downregulated and the expression of the NMDAR NR2B subunit was upregulated by ocular hypertension, and these effects of elevated intraocular pressure (IOP) were also prevented by PNU-282987.
Conclusions :
Retina GABAA and NMDAR expression and function are modulated positively and negatively, respectively, by activation of α7-nAChR in in vivo chronic glaucomatous models.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.