AIM:To explore the effect and significance of NEP1-40 on visual cortical plasticity of monocular deprivation in adult rats.

METHODS: Totally 60 neonatal rats were randomly allocated into 6 groups: normal animals(Nor), normal animals treated with PBS(Nor+PBS)or NEP1-40(Nor+NEP), MD animals without any treatment(MD), MD animals treated with PBS(MD + PBS)or NEP1-40(MD + NEP). We subjected P21 rats to monocular deprivation model until P45. Then the deprived eyes of MD model rats were reopened and followed by NEP1-40 or PBS administration for 7 days. Ultrastructral modifications of synaptic junctions and objective visual function were examined at P52 to determine the therapeutic effects of NEP1-40.

RESULTS: The objective visual function examined by F-VEP: At P45, F-VEP showed that compared with rats in Nor group, deprived eyes of rats in MD group, MD+PBS group and MD+NEP group displayed a longer latency(P<0.05)and a smaller amplitude(P<0.05); At P52, we could see that comparing with the MD group and MD + PBS group, the latencies of F-VEP in MD+NEP group were shortened and the amplitudes were increased(P<0.05), which were similar with that of in Nor group(Nor vs MD+NEP, P>0.05). The structural modifications of synaptic junctions examined by electromicrographs: All of the structural parameters of the synaptic junction in visual cortex were altered by monocular deprivation in MD group compared with the Nor group, displaying an increased width of synaptic clefts, shortened synaptic active zone, decreased curvature of synaptic interface and decreased thickness of PSD. However, synaptic ultrastructural analysis showed that NEP1-40 treatment could recover the entire structural index in monocular deprivation rats(MD vs MD+PBS vs MD+NEP, P<0.05)but not normal rats(Nor vs Nor+PBS vs Nor+NEP, P>0.05). It was noteworthy that, although the width of synaptic clefts in MD+NEP group decreased remarkably in comparison with that of in MD group, it still had not reach the normal level(Nor vs MD+NEP, P>0.05).

CONCLUSION: NEP1-40 could recover the structural modifications of synaptic junctions of neurons in visual cortex contralateral to deprived eye, as well as the objective visual function of deprived eye, which indicated a new role for NEP1-40 in reactivation of visual cortical plasticity from monocular deprivation in adult rats and offered the theoretical foundation for curing adult patients with amblyopia in the clinic.