Effects Of CNTF On The Long Distance Regeneration Of Axons With The Incomplete Injury Of Optic Nerve In Rats

Purpose To evaluate the effects of recombinant human Ciliary Neurotrophic Factor(rhCNTF) on the long distance regeneration of axons and the functional recovery with the moderate incomplete injury of optic nerve(ON) in rats.Methods Adult female Wistar rats were randomly divided into rhCNTF-treated and control groups. After the optic nerve of each right eye was crushed by micro forceps for 10 seconds at 1.5mm behind the eyeball, rhCNTF(2 μ g /2 μ 1) was injected into vitreous cavity of treated group while distilled water (2 μ 1) was done in control group. The intravitreous injections were repeated respectively on 1, 2, 4 and 8 weeks after injury. The rats were sacrificed on 1, 2, 4, 8 and 12 weeks after injury and the pathology changes of optic nerve were observed by light and electron microscope.Meanwhile we investigated the number of regenerating and degenerating axons at different distal to the site of injury. 2.GAP-43 expression in each optic nerve was detected with immunohistochemistry. 3.The axoplasmic transport was assessed by anterograde labeling with horseradish peroxidase (HRP).4. F-VEP examinations were performed before,immediately and every time point after injury.The datas were analyzed statistically with SPSS.Results 1.Acute inflammatory reaction and axons degeneration were observed on 1 and 2 weeks after injury.The scar formed in injury area and axons degeneration became increasingly severe from 4 to 12 weeks after injury and the number of axons in rhCNTF-treated group were more than that in control group. Plexiform regenerating unmyelinated fibers at 8mm and diffuse regrowing axons at 2mm distal to injury site were observed respectively in rhCNTF-treated group and control group. 2. The expressions of GAP-43 at the position distal to injury site in rhCNTF-treated group were higher than that in control from 4 to 12 weeks after the optic nerve injury. 3. The labeling density by HRP decreased immediately on 1 and 2 weeks and recovered obviously on 4 weeks after injury.The recovery ratios of axoplasmic transport in rhCNTF-treated group and control group were 31.86% and 12.87% respectively.There are significantly difference of the HRP anterograde labeling axons density in ON and superior colliculus between rhCNTF-treatedgroup and control groups on 4 to 12 weeks after injury.(p<0.01).4. F-VEP indicated that the mean latency recovered to the value before injury on the first week and the amplitude obviously recovered on 4 weeks after the injury. The recovery ratio of amplitude was 50.35% in rhCNTF-treated group, and 30.84% in control on 8 weeks after injury (p<0.01). Conclusions1. CNTF can effectively advance the long distance regeneration of axons and restoration of visual functions by activating the regenerating reaction, promoting the recovery of axoplasmic transport, and slowing underway degeneration of axons following the moderate incomplete injury of optic nerve in adult rats .2. It's also limited for CNTF to promote the regeneration of optic nerve.Many factors involved in the complicated process of regeneration of optic nerve. The comprehensive treatment will be more effective by upregulating the intrinsic growth potential of RGCs and overcoming the unfavorable extrinsic CNS environment.