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

Abstract

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. 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. The outer nuclear layer thickness was partially preserved in G-CSF-treated mice (measured at 300 microm superior from the optic disc, G-CSF: 14.9 +/- 6.3 microm versus control: 6.7 +/- 2.5 microm), and an electroretinogram confirmed the preservation of wave amplitudes (maximum scotopic a-wave G-CSF: 97.7 +/- 48.0 microV versus control: 14.4 +/- 21.9 microV, maximum scotopic b-wave G-CSF: 298.1 +/- 145.3 microV versus control: 33.2 +/- 50.1 microV). 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). 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.