Research Article| Volume 357, ISSUE 1-2, P157-166, October 15, 2015

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Neuregulin-1 protects against acute optic nerve injury in rat model


      • We investigated neuregulin-1 expression in optic never and retinal ganglion cells.
      • We constructed the classic acute optic nerve injury model.
      • Retinal ganglion cell numbers and apoptosis rate were made using TUNEL assay.
      • NRG-1 expression increased at first and then reduced after optic nerve injury in rats.
      • The protective effectiveness of NRG-1 might be correlated with its dosage.



      In this study, we employed a rat model and examined the expression pattern of neuregulin-1 (NRG-1) in optic nerve and retinal ganglion cells (RGCs) in response to optic nerve injury to understand the role of NRG-1 in conferring protection against acute optic nerve injury.


      Forty-eight male rats were randomly divided into two groups, the sham-operation group (n = 24) and optic nerve injury group (n = 24). Flash visual evoked potentials (FVEP) and fundography images were acquired at different time points following optic nerve injury (2 h, 1 d, 2 d, 7 d, 14 d and 28 d). Semi-quantitative analysis of NGR-1 expression pattern was performed by immunohistochemistry (IHC) staining. In a related experiment, 100 male rats were randomly divided into NGR-1 treatment group (n = 60) (treated with increasing dose of NGR-1 at 0.5 μg, 1 μg and 3 μg), normal saline (NS) group (n = 20) and negative control group (n = 20). Optic nerve injury was induced in all the animals and in situ cell death was measured by detecting the apoptosis rates using TUNEL assay.


      Fundus photography results revealed no detectable differences between the sham-operation group and optic nerve injury group at 2 h, 1 d, 2 d and 7 d. However at 2 weeks, the optic discs turned pale in all animals in the optic nerve injury group. NRG-1 expression increased significantly at all time points in the optic nerve injury group (P < 0.05), compared to the sham-operation group, with NRG-1 expression peaking at 14 d and gradually declining by 28 d. Statistically significant differences in amplitude and latency of P100 wave were also detected between the optic nerve injury and sham-operation group (P < 0.05). In related experiment, compared to NS group, treatment with 1 μg and 3 μg of recombinant human NRG-1 resulted in statistically significant FVEP-P100 amplitude values (all P < 0.05). Further, compared to the NS group, ganglion cell apoptosis was dramatically reduced in the NRG-1 group at all time points and the reduction was statistically significant in 3 μg NRG-1 treatment group at 7 d, 14 d and 28 d (all P < 0.05).


      Our results strongly suggest that NRG-1 is highly effective in preserving normal optic nerve function and is essential for tissue repair following optic nerve injury. Thus, NRG-1 expression confers protection against acute optic nerve injury in a dose-dependent manner.


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