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

Abstract

ObjectivesIn 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. MethodForty-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 (2h, 1d, 2d, 7d, 14d and 28d). 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 0.5μg, 1μg and 3μg), 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. ResultsFundus photography results revealed no detectable differences between the sham-operation group and optic nerve injury group at 2h, 1d, 2d and 7d. However at 2weeks, 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 14d and gradually declining by 28d. 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 1μg and 3μg 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 3μg NRG-1 treatment group at 7d, 14d and 28d (all P<0.05). ConclusionOur 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.