Highlights
- •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.
Abstract
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, 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.
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 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).
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.
Keywords
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Article info
Publication history
Published online: July 16, 2015
Accepted:
July 14,
2015
Received in revised form:
June 9,
2015
Received:
January 9,
2015
Identification
Copyright
© 2015 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
