Therapeutic effects of topical applications of ciliary neurotrophic factor (CNTF) on the injured optic nerve of adult rats. Ciliary neurotrophic factor (CNTF) induces differentiation of retinopetal dopaminergic neurons from mesencephalic precursor cells and affects regeneration of retinofugal fibers. Thus, CNTF is expected to exert beneficial effects on regeneration of the injured optic nerve. Our previous experiments indicated that daily topical applications of CNTF on the injured optic nerve of adult rats delayed degeneration of the optic nerve and retarded disappearance of RGCs. However, the extent of preservation of RGCs was modest in previous experiments. The present study attempted to apply an effective CNTF dose to the optic nerve. Our previous study indicated that the dose of 0.1 ng CNTF given topically could induce enough expression of tyrosine hydroxylase in the developing rat retina, but lower than this dose did not induce expression. In addition, an appropriate dose was able to regenerate axons from ganglion cell axons to the tectum in the adult rats. To identify the optimal dose, CNTF was applied daily to the crushed optic nerve for 2 weeks. An optimal dose was identified as 1.0 ng based on histological and morphological evaluations and counting of remaining RGCs at 3 weeks after the optic nerve injury. When the optic nerve was crushed, animals received daily topical application of 1.0 ng CNTF, and the other group of animals received vehicle solution as control. The retinofugal fibers failed to penetrate into the tectum in control animals, while many regenerating fibers were observed in CNTF-treated animals. Thus, the optimal dose of 1.0 ng CNTF may be an effective dose for preservation of RGCs and regenerating axons. The results indicate that the injured optic nerve can be rescued using appropriate doses of CNTF.