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Originally published In Press as doi:10.1167/iovs.08-1711 on August 1, 2008
(Investigative Ophthalmology and Visual Science. 2008;49:5629-5635.)
© 2008 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.08-1711

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Granulocyte Colony-Stimulating Factor Protects Retinal Photoreceptor Cells against Light-Induced Damage

Akio Oishi, Atsushi Otani, Manabu Sasahara, Hiroshi Kojima, Hajime Nakamura, Yuko Yodoi, and Nagahisa Yoshimura

From the Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan.

PURPOSE. Granulocyte colony stimulating factor (G-CSF) has been shown to have neuroprotective and anti-inflammatory effects in cerebral damage models. In addition, bone-marrow–derived hematopoietic cells, which can be mobilized with G-CSF, have a neuroprotective effect in hereditary retinal cell death. The present study was conducted to investigate whether G-CSF protects photoreceptors from light-induced cell death.

METHODS. G-CSF or vehicle was systemically injected before the light exposure and for four consecutive days after the exposure. Morphologic and electrophysiologic examinations were performed 1 week after the exposure to light. Gamma ray irradiation (6.5 Gy) was used to examine the involvement of bone marrow-derived cells increased by G-CSF injection. The expression of G-CSF receptor in the retina was analyzed by immunohistochemistry and quantitative RT-PCR.

RESULTS. The outer nuclear layer thickness was partially preserved in G-CSF–treated mice (measured at 300 µm superior from the optic disc, G-CSF: 14.9 ± 6.3 µm versus control: 6.7 ± 2.5 µm), and an electroretinogram confirmed the preservation of wave amplitudes (maximum scotopic a-wave G-CSF: 97.7 ± 48.0 µV versus control: 14.4 ± 21.9 µV, maximum scotopic b-wave G-CSF: 298.1 ± 145.3 µV versus control: 33.2 ± 50.1 µV). The effect was not lost, even with leukocyte depletion by irradiation. G-CSF receptor was expressed in retinal cells and upregulated by the light exposure (1.8-fold upregulation 2 hours after light exposure).

CONCLUSIONS. G-CSF protects photoreceptor cells against light-induced damage, possibly via G-CSF receptor expressed on retinal cells. These findings may lead to a novel treatment strategy for neural degenerating diseases of the retina.








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