Protective effects of the β3-adrenoceptor agonist CL316243 against N-methyl-D-aspartate-induced retinal neurotoxicity
Protective effects of the β3-adrenoceptor agonist CL316243 against N-methyl-D-aspartate-induced retinal neurotoxicity
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DOI：
10.1007/s00210-012-0796-1
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发表时间：
2012-11-01
影响因子：
3.6
通讯作者：
Ishii, Kunio
中科院分区：
文献类型：
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作者：
Oikawa, Fuka;Nakahara, Tsutomu;Ishii, Kunio
我们以前曾报道β 3肾上腺素受体激动剂扩张视网膜血管，但其对视网膜神经元的影响尚不清楚。在这项研究中，我们检查了β（3）-肾上腺素受体激动剂CL 316243对玻璃体内注射N-甲基-D-天冬氨酸（NMDA）诱导的大鼠视网膜损伤的作用。在玻璃体内注射NMDA之前、同时或之后将CL 316243注射到玻璃体腔中。注射NMDA后7天，观察到神经节细胞层（GCL）中的细胞丢失和内丛状层变薄。在注射NMDA后15、30、60或120 min注射CL 316243可减少GCL中细胞数量的减少，而在注射NMDA后240 min注射CL 316243时未观察到显著的保护作用。CL 316243预注射30 min或CL 316243与NMDA同时注射均无保护作用。β 3肾上腺素受体拮抗剂L748337在注射NMDA后120 min几乎完全消除了CL 316243的保护作用。在NMDA处理后1天检查的眼睛中，小清蛋白阳性无长突细胞的数量减少，但在NMDA注射后120 min注射CL 316243可防止这种情况。这些结果表明，CL 316243通过刺激β（3）-肾上腺素受体对NMDA诱导的损伤发挥保护作用。β（3）-肾上腺素能受体激动剂可能是治疗与谷氨酸诱导的兴奋性毒性相关的视网膜疾病（包括青光眼和糖尿病性视网膜病）的有效候选物。
We have previously reported that beta(3)-adrenoceptor agonists dilate retinal blood vessels, but their effects on retinal neurons have been unclear. In this study, we examined the action of the beta(3)-adrenoceptor agonist CL316243 against retinal damage induced by intravitreal injection of N-methyl-D-aspartate (NMDA) in rats. CL316243 was injected into the vitreous cavity before, with, or after intravitreal NMDA injection. Seven days after NMDA injection, cell loss in the ganglion cell layer (GCL) and thinning of the inner plexiform layer were observed. The reduction in the number of cells in the GCL was diminished by injection of CL316243 at 15, 30, 60, or 120 min after NMDA injection, whereas no significant protective effect was observed when CL316243 was administered 240 min after NMDA injection. Neither preinjection of CL316243 30 min before NMDA nor simultaneous injection of CL316243 with NMDA exerted any protective effect. The beta(3)-adrenoceptor antagonist L748337 almost completely abolished the protection conferred by CL316243 injection 120 min after NMDA injection. The number of parvalbumin-positive amacrine cells was decreased in eyes examined 1 day after NMDA treatment, but this was prevented by CL316243 injection at 120 min after NMDA injection. These results suggest that CL316243 exerts protective effects against NMDA-induced damage by stimulation of beta(3)-adrenoceptors. beta(3)-adrenoceptor agonists may be effective candidates for the treatment of retinal diseases associated with glutamate-induced excitotoxicity, including glaucoma and diabetic retinopathy.