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

Objectives: 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. Method: 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, 14d 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 NCR-1 treatment group (n = 60) (treated with increasing dose of NCR-1 at 0.5 mu g, 1 mu g and 3 mu g), 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. Results: 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 mu g and 3 mu g 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 mu g NRG-1 treatment group at 7 d, 14 d and 28 d (all P < 0.05). Conclusion: 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. (C) 2015 Elsevier B.V. All rights reserved.