Neurophysiological examination in relationship of glaucomatous neurodegeneration and glutamate neurotoxicity

青光眼神经变性与谷氨酸神经毒性关系的神经生理学检查

• 批准号: 07671921
• 负责人: MISHIMA Hiromu
• 金额: $ 1.34万
• 依托单位: HIROSHIMA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07671921/
• 关键词: Retinal culture; Neuronal death; Glutamate; Calcium ion; Patch-clamp; Acidosis; プロテインキナーゼC; 血管作動性腸管ペプチド

In 1995, we found that the activation of inositol phospholipid signaling pathway by PKC-related drugs deteriorated and the activation of adenylyl cyclase by vasoactive intestinal peptide (VIP) ameliorated glutamate neurotoxicity in retinal cultures. In 1996, we examined the dynamics of cytosolic Ca^<2+> concentration ([Ca^<2+>] i) by image analyzing system and the glutamate-induced inward current by whole-cell patch-clamp recordings, respectively, to elucidate the mechanisms of the effect of PKC-related drugs or VIP on glutamate-neurotoxicity. Using these procedure mentioned above, these drugs had no effect on glutamate-induced increase in [Ca^<2+>] i or glutamate-induced inward currents. Therefore, we speculated that PKC-related drugs and VIP affected the mechanisms of glutamate neurotoxicity at the downstream of glutamate receptor-activation.Furthermore, we found that the change of extracellular environment from pH 7.4 to acidic conditions (pH 6.0-7.0) protected cultured retinal neurons from glutamate neurotoxicity. In the electrophysiological examination using patch-clamp recording, N-methyl-D-aspartate (NMDA) receptor-activation was inhibited by extracellular acidic pH.Taken together, the acidic conditions protected cultured retinal neurons from glutamate neurotoxicity via suppression of NMDA receptor-activation.

1995年，我们发现PKC相关药物对肌醇磷脂信号通路的激活恶化，血管活性肠肽（VIP）对腺苷酸环化酶的激活减轻了视网膜培养中谷氨酸的神经毒性。1996年，我们分别用图像分析系统和全细胞膜片钳技术观察了细胞内Ca^<2 +>浓度（[Ca^<2+] i）的动态变化和谷氨酸诱导的内向电流，以阐明PKC相关药物或VIP对谷氨酸神经毒性的作用机制。使用上述方法，这些药物对谷氨酸诱导的[Ca^2+] i增加或谷氨酸诱导的内向电流没有影响。因此，我们推测PKC相关药物和VIP在谷氨酸受体激活的下游影响谷氨酸神经毒性的机制，并发现细胞外环境从pH 7.4到酸性（pH 6.0-7.0）的改变保护了培养的视网膜神经元免受谷氨酸神经毒性的影响。在膜片钳记录的电生理检查中，N-甲基-D-天冬氨酸（NMDA）受体激活被细胞外酸性pH抑制。总之，酸性条件通过抑制NMDA受体激活来保护培养的视网膜神经元免受谷氨酸神经毒性。

项目成果

Kosaka T., Mishima H.K., Kiuchi Y., Kataoka K.: "Effects of prostaglandins on the blood-ocular barrier." Jpn.J.Ophthalmol.39. 368-376 (1995)

Kosaka T.、Mishima H.K.、Kiuchi Y.、Kataoka K.：“前列腺素对血眼屏障的影响。”

Mishima H.K.: "Effects of prostaglandins on the blood-ocular barrier." Japanese Journal of Ophthalmology. 39. 368-376 (1995)

Mishima H.K.：“前列腺素对血眼屏障的影响。”

Mishima H.K.: "Ca^<2+>/calmodulin effects on cAMP response in cultured chick ciliary epithelial cells." Japanese Journal of Ophthalmology. 39. 317-322 (1995)

Mishima H.K.：“Ca ^ 2 /钙调蛋白对培养的鸡睫状上皮细胞中cAMP反应的影响。”

Mishima H.K.: "Ultrasound biomicroscopic study of ciliary body thicknesess of pharmacologic agents." American Journal of Ophthalmology. 121. 319-321 (1996)

Mishima H.K.：“药物制剂睫状体厚度的超声生物显微镜研究”。

Mishima H.K.: "Circadian intraocular pressure management with latanoprost : Diurnol and nocturnal intraocular pressure reduction and increased uveoscleral outflon" Survey of Ophthalmology. 41. 139-144 (1997)

Mishima H.K.：“拉坦前列素的昼夜眼压管理：Diurnol和夜间眼内压降低以及葡萄膜巩膜外流增加”眼科调查。