在眼压升高的 C57BL/6 小鼠眼中淀粉样前体蛋白和淀粉样-β的分布。
Distribution of amyloid precursor protein and amyloid-beta in ocular hypertensive C57BL/6 mouse eyes.
机构信息
Department of Ophthalmology, University of Bern, Bern, Switzerland.
出版信息
Curr Eye Res. 2010 Sep;35(9):828-34. doi: 10.3109/02713683.2010.494240.
PURPOSE
Amyloid precursor protein (APP) and amyloid-beta (Abeta) appear to participate in the pathophysiology of retinal ganglion cell (RGC) death in glaucoma. We, therefore, determined the distribution of APP and Abeta in the retinas of C57BL/6 mice after induction of chronic ocular hypertension.
METHODS
Ocular hypertension was induced in one eye of three-month-old C57BL/6 mice by injection of hypertonic saline into episcleral veins. After 6 weeks of documented elevated intraocular pressure (IOP), retinas were fixed with 4% paraformaldehyde and processed for immunohistochemistry with antibodies including a polyclonal antibody to the C-terminus of Abeta 40 (Novartis 17-40/23) and a polyclonal antibody to the APP ectodomain (Novartis 474). Distribution and semiquantitative expression of APP and Abeta immunolabeling in ocular hypertensive and control retinas were graded in a masked fashion and compared.
RESULTS
APP and Abeta immunoreactivity was found in the pia/dura, optic nerve (ON), and RGC layer of ocular hypertensive retinas, whereas APP and Abeta immunoreactivity in the contralateral control eyes was detected only in the pia/dura. Comparison of ocular hypertensive and control eyes for Abeta immunolabeling was significant in the ON and RGC layer (p < 0.05) whereas no significant difference was found when compared for APP staining.
CONCLUSIONS
High Abeta and APP levels were seen in ocular hypertensive retinas, probably due to abnormal APP-splicing in the presence of elevated IOP.
目的
淀粉样前体蛋白（APP）和β-淀粉样肽（Abeta）似乎参与了青光眼视网膜神经节细胞（RGC）死亡的病理生理学过程。因此，我们确定了在诱导慢性眼高压后 C57BL/6 小鼠视网膜中 APP 和 Abeta 的分布。
方法
通过向巩膜静脉内注射高渗盐水，在 3 个月大的 C57BL/6 小鼠的一只眼诱导眼高压。在记录到眼内压升高 6 周后，用 4%多聚甲醛固定视网膜，并使用包括针对 Abeta 40 羧基末端的多克隆抗体（诺华 17-40/23）和针对 APP 胞外域的多克隆抗体（诺华 474）的抗体进行免疫组织化学染色。以盲法方式对眼高压和对照视网膜中 APP 和 Abeta 免疫标记的分布和半定量表达进行分级，并进行比较。
结果
在眼高压视网膜的软脑膜/硬脑膜、视神经（ON）和 RGC 层中发现了 APP 和 Abeta 免疫反应性，而在对侧对照眼中的 APP 和 Abeta 免疫反应性仅在软脑膜/硬脑膜中检测到。ON 和 RGC 层中 Abeta 免疫标记的眼高压眼与对照眼之间的比较具有统计学意义（p<0.05），而 APP 染色的比较则无统计学差异。
结论
在眼高压视网膜中观察到高 Abeta 和 APP 水平，可能是由于在升高的 IOP 存在下 APP 剪接异常。
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