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Wei Wang, Sang Joon Lee, Guomin Jiang, Yongqing Liu, Ni Xu, Henry J Kaplan, Douglas C Dean; Granulocyte Colony Stimulation Factor (G-csf) Blocks Retinal Gliosis in a Mouse Model of Retinitis Pigmentosa. Invest. Ophthalmol. Vis. Sci. 2014;55(13):2269.
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The leading cause of blindness in western countries is retinal degeneration. In lower vertebrates, Muller glia proliferate in response to retinal damage and dedifferentiate to retinal photoreceptor progenitors, which in turn replace lost photoreceptors. But, in higher vertebrates Muller cells instead undergo a gliotic response leading to scar formation. Such gliotic responses are a hallmark of CNS injury where they not only inhibit tissue regeneration but also serve as a barrier to stem cell transplantation therapy. During photoreceptor degeneration, a glial scar forms between photoreceptors and the RPE, which acts as a barrier to subretinal transplantation of stem cell-derived photoreceptor progenitors. Granulocyte Colony Stimulation Factor (G-csf) is classically used to stimulate proliferation and survival of bone marrow progenitors in patients undergoing chemotherapy. But, G-csf also has well recognized antiapoptotic effects and it has been utilized as a neuroptotective agent in the retina and to protect cardiomyocytes in the heart. Here, we examined a potential role for G-csf on Müller cells in culture and in a mouse model of retinitis pigmentosa.
Mouse Müller cells were cultured on Matrigel in DMEM complete medium with 10% FBS. The cells were treated with 100 ng/mg G-csf for 5 or 10 days, then the cells were fixed and immunostaining Gfap as a marker of gliosis. rd10 mice were injected with G-csf and the effect on retinal gliosis was evaluated at various times histologically.
We found that Muller cells expressed the G-csf receptor, and that G-csf repressed expression of the gliotic marker Gfap in the cell in culture. In vivo, G-csf injection also blocked Muller cell expression of Gfap, and it prevented gliotic scar formation as photoreceptors degenerated in rd10 mice. .
Although glial cells are critical for neuronal survival, following CNS injury in higher vertebrates they express Gfap and produce a glial scar that constitutes a major block to tissue repair and to stem cell transplantation therapy. Our results suggest that G-csf represses Gfap and it inhibits retinal gliosis that occurs as photoreceptor degeneration occurs. Thus, G-csf might be an effective treatment to inhibit glial scarring and facilitate regeneration and stem cell transplantation therapy not only in the retina but in other CNS tissues damaged by injury or disease.
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