Reduction of Apoptosis in Ischemic Retinas of Two Mouse Models Using Hyperbaric Oxygen Treatment
Reduction of Apoptosis in Ischemic Retinas of Two Mouse Models Using Hyperbaric Oxygen Treatment
复制标题
DOI：
10.1167/iovs.11-7574
复制
发表时间：
2011-09-01
影响因子：
4.4
通讯作者：
Goldenberg-Cohen, Nitza
中科院分区：
文献类型：
--
作者：
Gaydar, Vera;Ezrachi, David;Goldenberg-Cohen, Nitza
目的.探讨高压氧（HBO）治疗对视网膜缺血模型小鼠的影响。在每只50只小鼠中诱导单侧视网膜中央动脉阻塞（CRAO）或视神经挤压（ONC），其中30只在受伤后立即接受2个大气压下的100%氧气治疗90分钟，然后每天治疗一次，持续长达14天。在第1、3和21天对小鼠实施安乐死，以进行组织学分析、凋亡测定和定量实时聚合酶链反应测试。结果进行了分析的损伤和治疗。HBO治疗使CRAO模型中的细胞损失从58%减少到30%，使ONC模型中的细胞损失从52%减少到32%。在这两种模型中，它与视网膜神经节细胞层中细胞存活的显著增加相关。在第1天HBO处理的CRAO小鼠中，促凋亡基因（bax，caspase-3）的表达水平最低限度地降低，但这种趋势在第3天逆转。在ONC组中，caspase-3、bax和bcl-x的水平在第1天增加，并在第3天降至基线以下。缺血和氧化应激相关基因（HO-1，SOD-1，GPX-1，NOX-2）表达水平的变化模式以及HBO治疗的有效性因模型而异。然而，总体而言，在未经治疗的小鼠中增加的基因表达水平在HBO治疗后进一步增加，而在HBO治疗后降低的基因表达水平进一步降低。HBO治疗可保护受损神经细胞免于凋亡。ONC或CRAO后对治疗的反应在分子上不同。这些结果将促进急性缺血性视网膜损伤的临床试验。（Invest Ophthalmol维斯科学。2011;52：7514-7522）DOI：10.1167/iovs.11-7574
PURPOSE. To investigate the effect of hyperbaric oxygen (HBO) chamber treatment in mouse models of retinal ischemia.METHODS. Unilateral central retinal artery occlusion (CRAO) or optic nerve crush (ONC) was induced in 50 mice each, of which 30 were treated with 100% oxygen at 2 atm for 90 minutes immediately after injury and then daily for up to 14 days. Mice were euthanatized on days 1, 3, and 21 for histologic analysis, apoptosis assay, and quantitative real-time polymerase chain reaction test. Findings were analyzed by injury and by treatment.RESULTS. HBO treatment reduced cell loss from 58% to 30% in the CRAO model and from 52% to 32% in the ONC model. In both models, it was associated with significantly increased cell survival in the retinal ganglion cell layer. Expression levels of the proapoptosis genes (bax, caspase-3) decreased minimally in the HBO-treated CRAO mice on day 1, but this trend was reversed on day 3. In the ONC group, levels of caspase-3, bax, and bcl-x increased on day 1 and dropped below baseline on day 3. The pattern of changes in the expression levels of the ischemia-and oxidative-stress-related genes (HO-1, SOD-1, GPX-1, NOX-2) and the effectiveness of HBO treatment varied by model. Overall, however, gene expression levels that increased in the untreated mice increased further with HBO treatment and levels that decreased, decreased further with treatment.CONCLUSIONS. HBO treatment protects injured neuronal cells from apoptosis. Response to treatment differs molecularly after ONC or CRAO. These results should prompt clinical trials of acute ischemic retinal damage. (Invest Ophthalmol Vis Sci. 2011;52:7514-7522) DOI:10.1167/iovs.11-7574