Decreased retinal neuronal cell death in caspase-1 knockout mice
Decreased retinal neuronal cell death in caspase-1 knockout mice
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DOI：
10.1007/s10384-006-0352-y
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发表时间：
2006-09-01
影响因子：
2.4
通讯作者：
Yoshimura, Nagahisa
中科院分区：
文献类型：
--
作者：
Arai, Jun;Katai, Naomichi;Yoshimura, Nagahisa
目的：方法：将8 ~ 10周龄的Caspase-1基因敲除小鼠（Casp 1（-/-））和野生型（WT）小鼠（C57 BL/6）暴露于25 000 lux的冷白色荧光灯下2 h。其他小鼠通过将眼内压升高至110 mmHg持续45分钟来经受视网膜缺血。在光暴露之前和之后记录视网膜电图（ERG）。用TUNEL法检测损伤后的凋亡细胞。测量视网膜内层厚度，评价缺血再灌注后视网膜的损伤情况。免疫组化和Western blotting检测caspase-1蛋白的表达。结果：Caspase 1（-/-）小鼠视网膜形态及ERG a、B波振幅与WT小鼠无明显差异。光暴露后，在WT小鼠视网膜的外核层中观察到TUNEL阳性细胞。光暴露后的TUNEL阳性感光细胞核的数量和缺血-再灌注损伤后的内核层中的细胞核的数量在Casp 1（-/-）小鼠中显著少于WT小鼠。光损伤后野生型小鼠视网膜光感受器细胞caspase-1阳性表达增多。结论：过度光暴露和缺血再灌注损伤后，Casp 1（-/-）小鼠视网膜神经元凋亡不明显。这些数据表明caspase-1在视网膜神经元凋亡中起作用。
Purpose: To determine whether apoptosis of retinal neurons induced by excessive light exposure and ischemia-reperfusion injury is altered in caspase-1 knockout mice.Methods: Eight- to 10-week-old caspase-1 knockout mice (Casp1(-/-)) and wild-type (WT) mice (C57BL/6) were exposed to diffuse, cool, white fluorescent light of 25 000 lux for 2 h. Other mice were subjected to retinal ischemia by increasing the intraocular pressure to 110mmHg for 45min. Electroretinograms (ERGs) were recorded before and after the light exposure. TdT-dUTP terminal nick-end labeling (TUNEL) was performed to identify the apoptotic cells after the insults. The inner retinal thickness was measured to evaluate the retinal injury after the ischemia-reperfusion. Expression of caspase-1 protein was studied by immunohistochemical analysis and Western blotting. Caspase-1-like protease activity was determined by a colorimetric tetrapeptide substrate.Results: The morphology of the retina and the amplitudes of the a and b waves of the ERGs of Casp1(-/-) mice did not differ from those of WT mice. After the light exposure, TUNEL-positive cells were observed in the outer nuclear layer of the WT mice retina. The number of TUNEL-positive photoreceptor nuclei after the light exposure, and the number of nuclei in the inner nuclear layer after the ischemia-reperfusion injury, were significantly less in Casp1(-/-) mice than in WT mice. There were more caspase-1-positive photoreceptor cells in WT mice after the light injury. The inner retinal layer of Casp1(-/-) mice significantly thicker in Casp1(-/-) mice than in WT mice 2 weeks after the ischemic insult.Conclusions: Retinal neuronal apoptosis was less prominent in Casp1(-/-) mice after excessive light exposure and ischemia-reperfusion injury. These data indicate that caspase-1 plays a role in retinal neuronal apoptosis.