Chemotactic Effect of Ciliary Neurotrophic Factor on Macrophages in Retinal Ganglion Cell Survival and Axonal Regeneration

作者：Ling‐Ping Cen, Jian-Min Luo, Chengwu Zhang, You‐Ming Fan, Yue Song, Kwok‐Fai So, Nico van Rooijen, Chi Pui Pang, Dennis S.C. Lam, Qi Cui · 发表于：Investigative Ophthalmology & Visual Science · 年份：2007 · DOI：10.1167/iovs.06-0791 · 被引用次数：84 · 研究领域：Nerve injury and regeneration、Neurogenesis and neuroplasticity mechanisms、Retinal Development and Disorders

PURPOSE: To examine whether ciliary neurotrophic factor (CNTF) has a chemotactic effect on macrophages and whether macrophages are involved in CNTF-induced retinal ganglion cell (RGC) survival and axonal regeneration after optic nerve (ON) injury. METHODS: Adult Fischer 344 rats received an autologous peripheral nerve graft onto transected ON for injured axons to grow. CNTF was applied intravitreally. When needed, clodronate liposomes were applied intravitreally or intravenously to deplete macrophages in the eye. A chemotaxis microchamber system was used to examine whether CNTF has a chemotactic effect on macrophages in vitro, whereas immunohistochemistry was used to identify the location of macrophages/microglia in the retina. The effects of CNTF on RGC neurite outgrowth and macrophage/microglia proliferation were tested in retinal explants. RESULTS: Intravitreal CNTF significantly enhanced RGC survival and axonal regeneration as well as the number of macrophages in the eye. Removal of macrophages significantly reduced CNTF-induced RGC survival and axon regeneration. A chemotaxis assay showed a clear chemotactic effect of CNTF on blood-derived but not peritoneal macrophages. Immunohistochemistry revealed that local microglia was located in a region from the nerve fiber layer (NFL) to the inner nuclear layer, whereas blood-derived macrophages were in the NFL. In vitro experiments revealed that CNTF did not enhance neurite outgrowth or macrophage/microglia proliferation in ret...