Protective effects of nerve growth factor against retinal ganglion cell damage in demyelinated optic neuritis in mice

Abstract

Objective To investigate the protective effects of nerve growth factor (NGF) against retinal ganglion cell (RGC) damage in demyelinated optic neuritis in mice. Methods Experimental study. Fifty C57BL/6 mice were randomly divided into 3 groups: the NGF-treated group (NGF), the balanced salt solution group (BSS), and the control group (CON). The right eye was used as the experimental eye. Optic neuritis and experimental autoimmune encephalomyelitis (EAE) were induced in the mice by subcutaneously injecting MOG35-55 peptide and complete Freund's adjuvant (CFA) in the NGF and BSS groups. NGF (3 μg/2 μl) was intravitrealy injected into the right eyes of the NGF group and BSS (2 μl) was intravitreally injected into the right eyes of the BSS group on days 4 and 10 post-immunization. Flash visual evoked potential (f-VEP) and flash electroretinogram (f-ERG)responses were recorded on days 0, 7 and 14 in all groups. After examination by visual electrophysiology, histological evaluation was performed. Consecutive sections of optic nerve were stained with hymatoxylin-eosin, Luxol fast blue and Bielschowsky silver impregnation to assess inflammation, demyelination, and axonal pathology. Apoptosis of RGC was measured by the TUNEL technique. The t-test was used to analyze the data of NGF and BSS groups. Results The clinical score and weight in the NGF group and BSS group did not change (t=-1.844, P=0.079;t=-2.012, P=0.059). At all times, the results of the f-VEP in the NGF group were not significantly different from f-VEP in the BSS group (P＞0.05). The ERG amplitude and latency of the b-wave were significantly different from the BSS group at day 14 after immunization (t=5.909, P=0.000; t=3.602,P=0.043). LFB staining showed that the areas of demyelination in the NGF and BSS groups were (31.50±8.72)% and (29.91±10.00)%, respectively; there was no singnificant difference between the two groups (t=0.298, P=0.709). At the same time, TUNEL assay showed the apoptotic index of RGC [(15.18±3.36)%] in the NGF group was significantly lower than that in the BSS group [(34.14±3.83)%)](t=11.790, P=0.000). Conclusion NGF has no significant effect on clinical score or degree of demyelination in mice. It can not decrease the incidence of disease, but treatment with NGF shows a protective effect on the survival and function of RGC. Key words: Nerve growth factor; Encephalomyelitis,autoimmune, experimental; Optic neuritis; Visual electrophysiology; Retinal ganglion cell; Disease models,animal