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Megumi Honjo, Hidenobu Tanihara, Noriaki Kido, Masaru Inatani, Kazushiro Okazaki, Yoshihito Honda; Expression of Ciliary Neurotrophic Factor Activated by Retinal Müller Cells in Eyes with NMDA- and Kainic Acid–Induced Neuronal Death. Invest. Ophthalmol. Vis. Sci. 2000;41(2):552-560.
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purpose. To elucidate the role of retinal Müller cells in
N-methyl-d-aspartate (NMDA)- or kainic acid
(KA)-induced retinal damage.
methods. In experimental eyes, NMDA or KA was injected into the vitreous of rat
eyes. Immunohistochemistry and western blot analysis were conducted to
elucidate expression and localization of glial fibrillary acidic
protein (GFAP) and ciliary neurotrophic factor (CNTF). In addition, the
neuroprotective effects of CNTF were calculated by counting cells in
the ganglion cell layer (GCL) and by measuring the thickness of the
various retinal layers.
results. Morphometric analysis of retinal damage in NMDA- and KA-injected eyes
showed significant cell loss in the GCL and thinning of the inner
plexiform layer (IPL) of the retina, but not of other retinal layers.
Immunohistochemistry demonstrated disappearance and/or decrease in
immunoreactivities of calbindin- and calretinin- positive cells and
their neurites and upregulated expression of both GFAP and CNTF in
experimental eyes. Western blot analysis showed an increase in protein
expression for CNTF in retinas of experimental eyes. Confocal images
and sequential localization demonstrated colocalization of CNTF and
GFAP in the inner retinal layer and possibly in Müller cells. In
addition, pretreatment with CNTF (1 μg) before the intravitreal
injection of NMDA (or KA) demonstrated that CNTF has neuroprotective
effects against NMDA- or KA-induced neuronal death in the retina.
conclusions. These studies revealed the upregulated expression of CNTF and GFAP in
Müller cells in response to NMDA- and KA-induced neuronal death,
suggesting that production of CNTF in Müller cells may be a part
of the endogenous neuroprotective system in the
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