Minocycline partially inhibits caspase-3 activation and photoreceptor degeneration after photic injury
Minocycline partially inhibits caspase-3 activation and photoreceptor degeneration after photic injury
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DOI：
10.1159/000086610
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发表时间：
2005-01-01
影响因子：
2.1
通讯作者：
Liao, CL
中科院分区：
文献类型：
--
作者：
Chang, CJ;Cherng, CH;Liao, CL
目的：探讨caspase-3在视网膜光损伤中的作用，并观察米诺环素是否能改善光诱导的光感受器变性。方法：采用强光照射诱导大鼠视网膜光损伤模型。采用Western blot、免疫组化和酶活性测定等方法检测caspase-3的表达。TUNEL法检测光感受器细胞凋亡。将大鼠随机分为治疗前和治疗后两组，在光损伤前或光损伤后给予米诺环素（15，30或45 mg/kg）。通过Western印迹、酶活性测定、TUNEL染色定量计数、外核层（ONL）厚度的形态计量学和组织病理学检查比较米诺环素和溶剂处理的视网膜光损伤。结果如下：光暴露后，活性caspase-3和多聚腺苷二磷酸核糖聚合酶在视网膜中上调，并在ONL中观察到caspase-3免疫反应性增加。Caspase-3酶活性增加，经历光损伤的视网膜，并在米诺环素预处理（30和45 mg/kg）和后处理（45 mg/kg）组，这种增加显着减少。通过定量TUNEL计数评估，在大鼠光损伤之前或之后腹腔内注射米诺环素也会导致TUNEL阳性光感受器减少。通过光损伤后14天ONL厚度测量的视网膜变性程度在米诺环素预处理（45 mg/kg）的大鼠中显著改善。结论：我们证明，增加caspase-3的活动本地化特定的光损伤后ONL内，米诺环素部分抑制caspase-3的激活和感光细胞变性在这个动物模型。版权所有（C）2005 S. Karger AG，巴塞尔。
Purpose: To evaluate the possible role of caspase-3 in retinal photic injury, and to investigate whether minocycline can ameliorate light-induced photoreceptor degeneration. Methods: Retinal photic injury was induced in rats by exposure to intense light. Expression of caspase-3 was studied using Western blot analysis, immunohistochemical staining and enzyme activity assay. Apoptotic photoreceptor cells were detected by the TdT-dUTP terminal nick-end labeling (TUNEL) method. Minocycline (15, 30 or 45 mg/kg) was administered before or after photic injury in rats randomly assigned to pretreatment and posttreatment groups. Minocycline and vehicle-treated retinas subjected to photic injury were compared with respect to Western blotting, enzyme activity assay, quantitative counts of TUNEL stains, morphometry of the outer nuclear layer (ONL) thickness and histopathological examination. Results: After light exposure, active caspase-3 and poly-adenosine diphosphate-ribose-polymerase were upregulated in the retinas and increased caspase-3 immunoreactivity was observed in the ONL. Caspase-3 enzyme activity increased in the retinas that underwent photic injury, and this increase was significantly reduced in minocycline pretreated (30 and 45 mg/kg) and posttreated (45 mg/kg) groups. Intraperitoneal administration of minocycline before or after photic injury in rats also resulted in less TUNEL-positive photoreceptors, as assessed by the quantitative TUNEL counts. The degree of retinal degeneration, measured by the ONL thickness 14 days after photic injury, was significantly improved in minocycline pretreatment (45 mg/kg) rats. Conclusions: We demonstrate that increased caspase-3 activities localize specifically within the ONL after photic injury, and that minocycline partially inhibits caspase-3 activation and photoreceptor degeneration in this animal model. Copyright (C) 2005 S. Karger AG, Basel.