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Involvement of endoplasmic reticulum stress on neuronal cell death in the lateral geniculate nucleus in the monkey glaucoma model
Author(s) -
Ito Yasushi,
Shimazawa Masamitsu,
Inokuchi Yuta,
Yamanaka Hajime,
Tsuruma Kazuhiro,
Imamura Kazuyuki,
Onoe Hirotaka,
Watanabe Yasuyoshi,
Aihara Makoto,
Araie Makoto,
Hara Hideaki
Publication year - 2011
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2010.07578.x
Subject(s) - endoplasmic reticulum , lateral geniculate nucleus , biology , retina , tunel assay , programmed cell death , neuroscience , microbiology and biotechnology , apoptosis , biochemistry
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 2α (p‐eIF2α) 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‐eIF2α 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.