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

¹From the Joint Shantou International Eye Center of Shantou University and The Chinese University of Hong Kong, Shantou University Medical College, Shantou, Peoples Republic of China; the ²Department of Ophthalmology and Visual Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, Peoples Republic of China; the ³Laboratory for Neural Repair, Shantou University Medical College, Shantou, Peoples Republic of China; ⁴Department of Anatomy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, Peoples Republic of China; and the ⁵Department of Cell Biology and Immunology, Faculty of Medicine, Vrije Universiteit, Amsterdam, The Netherlands.

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 retinal explants.

CONCLUSIONS. CNTF is a chemoattractant but not a proliferation enhancer for blood-derived macrophages, and blood-borne macrophages recruited into the eye by CNTF participate in RGC protection. This finding thus adds an important category to the existing understanding of the biological actions of CNTF.

This article has been cited by other articles:

				Q. Cui, L. Benowitz, and Y. Yin Does CNTF mediate the effect of intraocular inflammation on optic nerve regeneration? Brain, June 1, 2008; 131(6): e96 - e96. [Full Text] [PDF]

				D. Fischer CNTF, a key factor mediating the beneficial effects of inflammatory reactions in the eye Brain, June 1, 2008; 131(6): e97 - e97. [Full Text] [PDF]