Involvement of endoplasmic reticulum stress on neuronal cell death in the lateral geniculate nucleus in the monkey glaucoma model
Involvement of endoplasmic reticulum stress on neuronal cell death in the lateral geniculate nucleus in the monkey glaucoma model
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DOI：
10.1111/j.1460-9568.2010.07578.x
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发表时间：
2011-03-01
影响因子：
3.4
通讯作者：
Hara, Hideaki
中科院分区：
文献类型：
--
作者：
Ito, Yasushi;Shimazawa, Masamitsu;Hara, Hideaki
我们研究了内质网（ER）应激是否参与了眼内压（IOP）升高后外侧膝状体（LGN）神经元死亡的病理生理机制。对5只食蟹猴进行了研究，其中4只在激光光凝治疗后患有青光眼左眼，1只正常猴。在激光光凝治疗后4、11、15和24周，使用抗小白蛋白抗体免疫化学评价LGN神经元的数量和萎缩，所述抗体用于特异性标记连接至视皮层的中继神经元。此外，末端脱氧核苷酸转移酶介导的dUTP缺口末端标记（TUNEL）阳性细胞，多聚泛素和ER应激相关蛋白的产生，如真核起始因子2 α（p-eIF 2 α）和C/EBP同源蛋白（CHOP）的磷酸化，也使用原位杂交和免疫染色进行测量。激光光凝治疗后4-24周，对侧LGN第1、4、6层神经元丢失和/或萎缩。此外，来自高IOP眼的视网膜输入投射到同侧的第2层（大细胞层）、第3层和第5层（小细胞层）。在这些层中也证实了神经元损伤。在LGN区域，在激光光凝治疗后11-24周还检测到TUNEL阳性细胞、多聚泛素、p-eIF 2 α和CHOP。这些结果表明，ER应激可能在眼压升高后LGN神经元死亡中起关键作用。
We investigated whether endoplasmic reticulum (ER) stress was involved in the pathophysiological mechanisms underlying neuronal death of the lateral geniculate nucleus (LGN) after intraocular pressure (IOP) elevation. Five cynomolgus monkeys, four with a glaucomatous left eye after laser photocoagulation treatment and one normal monkey, were studied. At 4, 11, 15 and 24 weeks after the laser photocoagulation treatment, the numbers of LGN neurons and atrophy were immunohistochemically evaluated using anti-parvalbumin-antibody, which was used to specifically label relay neurons connecting to the visual cortex. In addition, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive cells, polyubiquitin, and production of ER stress-related proteins, such as the phosphorylation of eukaryotic initiation factor 2 alpha (p-eIF2 alpha) and C/EBP-homologous protein (CHOP), were also measured using in situ hybridization and immunostaining. Loss of neurons and/or neuronal atrophy in layers 1, 4 and 6 of the LGN on the contralateral side were observed at 4-24 weeks after the laser photocoagulation treatment. Furthermore, the retinal input from the high IOP eye projected to layers 2 (magnocellular layer), 3 and 5 (parvocellular layer) on the ipsilateral side. Neuronal damage was also confirmed in these layers. In the LGN region, TUNEL-positive cells, polyubiquitin, p-eIF2 alpha and CHOP were also detected at 11-24 weeks after the laser photocoagulation treatment. These findings indicate that ER stress may play a pivotal role in neuronal death of the LGN after IOP elevation.