Department of Systems Biology, University of Alcalá, 28871 Madrid, Spain.
Department of Physiology, Genetics and Microbiology. University of Alicante, 03690 Alicante, Spain.
Int J Mol Sci. 2020 Feb 25;21(5):1570. doi: 10.3390/ijms21051570.
Combined administration of N-Methyl-D-Aspartate (NMDA) and kainic acid (KA) on the inner retina was studied as a model of excitotoxicity. The right eye of C57BL6J mice was injected with 1 µL of PBS containing NMDA 30 mM and KA 10 mM. Only PBS was injected in the left eye. One week after intraocular injection, electroretinogram recordings and immunohistochemistry were performed on both eyes. Retinal ganglion cell (RGC) projections were studied by fluorescent-cholerotoxin anterograde labeling. A clear decrease of the retinal "b" wave amplitude, both in scotopic and photopic conditions, was observed in the eyes injected with NMDA/KA. No significant effect on the "a" wave amplitude was observed, indicating the preservation of photoreceptors. Immunocytochemical labeling showed no effects on the outer nuclear layer, but a significant thinning on the inner retinal layers, thus indicating that NMDA and KA induce a deleterious effect on bipolar, amacrine and ganglion cells. Anterograde tracing of the visual pathway after NMDA and KA injection showed the absence of RGC projections to the contralateral superior colliculus and lateral geniculate nucleus. We conclude that glutamate receptor agonists, NMDA and KA, induce a deleterious effect of the inner retina when injected together into the vitreous chamber.
将 N-甲基-D-天冬氨酸（NMDA）和海人酸（KA）联合注入内视网膜，作为兴奋性毒性模型进行研究。将 C57BL6J 小鼠的右眼注射 1 µL 含有 30 mM NMDA 和 10 mM KA 的 PBS。左眼仅注射 PBS。眼内注射后 1 周，对双眼进行视网膜电图记录和免疫组织化学检查。通过荧光霍乱毒素顺行标记研究视网膜神经节细胞（RGC）的投射。NMDA/KA 注射眼的视网膜“b”波振幅明显降低，无论是在暗适应还是明适应条件下。“a”波振幅没有明显影响，表明光感受器保持完好。免疫细胞化学标记显示外核层没有影响，但内视网膜层明显变薄，表明 NMDA 和 KA 对内双极细胞、无长突细胞和节细胞产生有害影响。NMDA 和 KA 注射后的视觉通路顺行追踪显示，RGC 投射到对侧上丘和外侧膝状体核的缺失。我们得出结论，当将谷氨酸受体激动剂 NMDA 和 KA 一起注入玻璃体腔时，会对内视网膜产生有害影响。
