Brimonidine protects against loss of Thy-1 promoter activation following optic nerve crush.

Brimonidine protects against loss of Thy-1 promoter activation following optic nerve crush.
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溴莫尼定可防止视神经挤压后 Thy-1 启动子激活丧失

DOI:
10.1186/1471-2415-13-26
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发表时间:
2013-06-27
期刊:
影响因子:
2
通讯作者:
Weinreb RN
Weinreb RN
中科院分区:
医学4区
文献类型:
--
作者:
Dai Y;Lindsey JD;Duong-Polk KX;Chindasub P;Leung CK;Weinreb RN

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研究背景视神经损伤后Thy-1表达的RGCs的丢失有一个快速下降的初期,然后是一个较长的下降速度较慢的时期。本研究使用纵向视网膜成像的小鼠表达青色荧光蛋白的控制下的Thy-1启动子(Thy 1-CFP小鼠),以确定如何α2-肾上腺素能激动剂溴莫尼定影响损失的Thy 1启动子activation.MethodsBaseline图像的荧光视网膜神经元在30 Thy 1-CFP小鼠获得使用改进的共聚焦扫描激光检眼镜。接下来,视神经挤压后立即给予溴莫尼定(100 ug/kg,IP)一次,或视神经挤压后立即给予,然后每2天给药一次,持续4周。对照组在视神经挤压后立即接受单次生理盐水注射。所有动物在视神经挤压后每周成像一次,持续四周。通过计数确定特定视网膜区域内荧光视网膜神经元的损失。ResultsAt one week after optic nerve crush,荧光视网膜神经元保留荧光的比例为对照小鼠基线的44±7%,一次溴莫尼定治疗后为51±6%,溴莫尼定治疗后每隔一天为55±6%(两个溴莫尼定治疗组与对照组相比P<0. 05)。随后,接受一次治疗的组中荧光视网膜神经元的数量与对照组无显著差异。相比之下,接受溴莫尼定重复治疗的组中荧光视网膜神经元的数量在挤压后两周比对照组多28%,在挤压后三周多32%(在两个时间点P<0.05)。速率分析显示,溴莫尼定减缓了多次给药动物荧光细胞下降的初始速率(P<0.05)。治疗组之间的损失率的差异不显着后,第二week.ConclusionRepeated溴莫尼定治疗保护荧光视网膜神经元内的Thy 1-CFP小鼠视神经粉碎后的荧光损失。由于该系统中的大多数荧光视网膜神经元是RGC,这些发现表明重复溴莫尼定治疗可以保护视神经挤压后的RGC健康。
BackgroundThe loss of RGCs expressing Thy-1 after optic nerve injury has an initial phase of rapid decline followed by a longer phase with slower reduction rate. This study used longitudinal retinal imaging of mice expressing cyan fluorescent protein under control of the Thy-1 promoter (Thy1-CFP mice) to determine how the α2-adrenergic agonist brimonidine influences loss of Thy1 promoter activation.MethodsBaseline images of the fluorescent retinal neurons in 30 Thy1-CFP mice were obtained using a modified confocal scanning laser ophthalmoscope. Next, brimonidine (100 ug/kg, IP) was administered either one time immediately after optic nerve crush, or immediately after optic nerve crush and then every 2 days for four weeks. A control group received a single saline injection immediately after optic nerve crush. All animals were imaged weekly for four weeks after optic nerve crush. Loss of fluorescent retinal neurons within specific retinal areas was determined by counting.ResultsAt one week after optic nerve crush, the proportion of fluorescent retinal neurons retaining fluorescence was 44±7% of baseline in control mice, 51±6% after one brimonidine treatment, and 55±6% after brimonidine treatment every other day (P<0.05 for both brimonidine treatment groups compared to the control group). Subsequently, the number of fluorescent retinal neurons in the group that received one treatment differed insignificantly from the control group. In contrast, the number of fluorescent retinal neurons in the group that received repeated brimonidine treatments was greater than the control group by 28% at two weeks after crush and by 32% at three weeks after crush (P<0.05 at both time points). Rate analysis showed that brimonidine slowed the initial rate of fluorescent cell decline in the animals that received multiple treatments (P<0.05). Differences in the rate of loss among the treatment groups were insignificant after the second week.ConclusionRepeated brimonidine treatments protect against loss of fluorescence within fluorescent retinal neurons of Thy1-CFP mice after optic nerve crush. As most of fluorescent retinal neurons in this system are RGCs, these findings indicate that repeated brimonidine treatments may protect RGC health following optic nerve crush.
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发表时间: 2009-11
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作者:
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