Induction of amyloid-β1-42 in the retina and optic nerve head of chronic ocular hypertensive monkeys
Induction of amyloid-β1-42 in the retina and optic nerve head of chronic ocular hypertensive monkeys
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发表时间：
2012-10
期刊：
影响因子：
2.2
通讯作者：
Yasushi Ito;M. Shimazawa;K. Tsuruma;C. Mayama;K. Ishii;H. Onoe;M. Aihara;M. Araie;H. Hara
中科院分区：
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作者：
Yasushi Ito;M. Shimazawa;K. Tsuruma;C. Mayama;K. Ishii;H. Onoe;M. Aihara;M. Araie;H. Hara
目的近年来的研究表明，淀粉样蛋白β1-42（Aβ1-42）的积累不仅与阿尔茨海默病（Alzheimer disease，AD）的发生发展有关，而且可能是青光眼视网膜神经节细胞死亡的原因之一。本研究旨在观察Aβ1-42在实验性青光眼猴视网膜和视神经乳头（ONH）中的表达和定位。方法采用免疫组织化学方法对5只食蟹猴激光治疗后4、9、11、15和24周的左眼青光眼进行研究。另取2只激光光凝治疗后133周左眼青光眼的食蟹猴，采用酶联免疫吸附法测定视网膜Aβ1-42浓度。结果激光光凝后11 ~ 24周，Aβ1-42在视网膜神经纤维层（NFL）、神经节细胞层（GCL）和ONH中表达上调，而淀粉样前体蛋白在NFL和ONH中的表达较9周时有所下降。Aβ1-42的定位在胶质细胞酸性蛋白阳性星形胶质细胞中合并，但在视网膜和ONH中磷酸化神经丝重链或非磷酸化神经丝重链阳性轴突中不合并。同样，猴子视网膜中的Aβ1-42浓度在青光眼慢性期增加。结论猴眼内压升高后Aβ1-42表达上调，其ONH结构与人类相似。
Purpose Recent studies have indicated that accumulation of amyloid β1–42 (Aβ1–42), which is associated with the progression of Alzheimer disease, may also be responsible for retinal ganglion cell death in glaucoma. The purpose of this study was to investigate the expression and localization of Aβ1–42 in the retina and the optic nerve head (ONH) of monkeys with experimental glaucoma. Methods Five cynomolgus monkeys with a glaucomatous left eye at 4, 9, 11, 15, and 24 weeks after laser photocoagulation treatment were studied by immunohistochemical methods. Another two cynomolgus monkeys with a glaucomatous left eye at 133 weeks after laser photocoagulation treatment were used to measure Aβ1–42 concentrations in the retina by enzyme-linked immunosorbent assay. Results At 11 to 24 weeks after the laser photocoagulation treatment, Aβ1–42 was upregulated in the nerve fiber layer (NFL) and the ganglion cell layer (GCL) of the retina and the ONH, but the expression of amyloid precursor protein decreased in the NFL and ONH from levels at 9 weeks. The localizations of Aβ1–42 were merged in glial fibrillary acidic protein-positive astroglial cells but not phosphorylated neurofilament heavy- or nonphosphorylated neurofilament heavy-positive axons in the retina and the ONH. Likewise, Aβ1–42 concentrations in the retina of monkeys increased in the chronic stage of glaucoma. Conclusions These findings indicate that the upregulation of Aβ1–42 after an intraocular pressure elevation could apply to monkeys since the structure of the ONH is more similar to humans than that of rodents.