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L.-P. Cen, C.-W. Zhang, N. van Rooijen, C. Pang, Q. Cui; Chemotactic Effect of Ciliary Neurotrophic Factor on Macrophages in Retinal Ganglion Cell Survival and Axonal Regeneration. Invest. Ophthalmol. Vis. Sci. 2007;48(13):236.
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To examine whether ciliary neurotrophic factor (CNTF) has chemotactic effect on macrophages and whether macrophages are recruited into the eye by CNTF to participate in CNTF-induced retinal ganglion cell (RGC) survival and axonal regeneration after optic nerve injury.
Experiments were carried out in adult Fischer 344 rats. Rats received an autologous peripheral nerve graft onto transected optic nerve for injured axons to grow. CNTF (1.5µg in 3µl) was applied intravitreally at 3, 9 and 15 days after optic nerve injury. When needed, clodronate liposomes were applied to deplete macrophages in the eye. Chemotaxis microchamber system was used to examine whether CNTF exerted chemotactic action on macrophages in vitro. Retinal explants were used to examine the effect of CNTF on RGC viability and neurite outgrowth in the environment whereby supply of blood-borne macrophages were not available. BrdU labeling was used to examine whether CNTF enhanced macrophage proliferation.
Intravitreal CNTF significantly enhanced the number of macrophages in the eye and promoted RGC survival and axonal regeneration after optic nerve injury. Removal of macrophages substantially reduced CNTF-induced RGC survival and axon regeneration. Macrophage migration assay showed that CNTF had a chemotactic effect on blood-derived but not peritoneal macrophages.In vitro experiments revealed that CNTF did not enhance neurite outgrowth in retinal explants. In addition, BrdU labeling revealed that CNTF did not enhance macrophage/microglial proliferation in vitro.
This study demonstrates that CNTF is a chemoattractant but not a proliferation enhancer for blood-borne macrophages that are known to invade into the eye after optic nerve injury, and the macrophages are recruited into the eye to participate in CNTF-induced RGC survival and axon regeneration. These findings thus add an important new category to our existing knowledge of biological actions of CNTF and macrophages.
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