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Ying Xu, Zongqin Xiang, Yiqin Bao, Jia Zhang, Jun Dong, Yibo Qu; Inhibition of non-NMDA ionotropic glutamate receptors delays the retinal degeneration in rd10 mouse. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5282.
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© ARVO (1962-2015); The Authors (2016-present)
Retinitis pigmentosa (RP) is a progressive neurodegenerative disease that causes deterioration of rod and cone photoreceptors, eventually leading to blindness. Retinal ganglion cells (RGCs) in animal models of RP exhibit an abnormally high spontaneous activity which interferes with signal processing; and blocking AMPA/Kainate receptors by bath application of CNQX decreases these spontaneous firing. Thus we wondered whether blocking these receptors in vivo may protect the function of inner retinal neurons during photoreceptor degeneration in rd10 mice, a model of RP.
We used immunostaining to detect changes of iGluRs expression in retina during photoreceptor degeneration. Then we used multi-electrode-array (MEA) system to record light responses of RGCs and the effects of perfusing low dose of CNQX. Lastly, we i.p. injected rd10 mice with CNQX or GYK152466 (specific AMPA receptor blocker) for 2 weeks, and examined the retinal functions and morphology, as well as their visual behavior.
Our data showed that iGluRs were up-regulated in the inner plexiform layer of rd10 retina. Both in vitro and in vivo application of low-dose CNQX inhibited the abnormal spontaneous spiking in all classes of RGCs and it increased the light evoked response of ON ganglion cells.GYK152466 had little effect. CNQX application also resulted in an improved behavioral performance. Surprisingly, in vivo application of CNQX slowed down photoreceptors degeneration as seen by an increase of their number and improvement of their structure. It also improved the structure of bipolar cells.
Our data suggests that blocking the non-NMDA iGluRs slows down the deterioration of RGCs function during photoreceptor degeneration by two independent mechanisms: by delaying photoreceptor degeneration and by directly affecting signal processing in the inner plexiform layer. Therefore it might be an effective strategy to extend the time window for treating RP.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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