Model making of radioactive optic nerve injury

Background

Radiation-induced optic neuropathy (RION) is a severe complication after radiotherapy for head and neck cancer, which threatens the visual acuity and quality of life of patients.Till now, there is no recognized treatment for RION.It is of great significance to study the natural progression of the RION, and to prevent and treat RION.

Objective

This study was to establish an ideal radioactive optic nerve injury animal model.

Methods

Healthy 8-week SD rats with hygiene grade were randomly divided into normal control group and model group, with 6 rats in each group.The total 30 Gy dose of radiation with 3 portions was used to irradiate the head model group rats; ELISA was performed to analysis the changes of endothelin-1 (ET-1) and Von Willebrand factor (vWF) concentrations in blood 2, 4 and 8 weeks after irradiation.Hematoxylin-eosin staining and transmission electron microscope were performed to observe the changes of optic structure.The use and care of the experimental animals complied with the ARVO statement.

Results

The concentrations of ET-1 in the model group were (23.18±0.11), (27.98±0.22), (33.90±0.11), (65.25±0.38) and (43.82±0.09)pg/ml before irradiation, 1 day, 2, 4, 6 weeks after irradiation, those in the normal control group were (22.65±0.14), (23.18±0.19), (23.68±0.15), (24.23±0.12) and (23.58±0.16)pg/ml.The concentrations of vWF in the model group were (63.16±2.21), (88.32±2.06), (123.38±1.36), (191.40±0.61) and (141.69±0.82)pg/ml before irradiation, 1 day, 2, 4, 6 weeks after irradiation, those in the normal control group were (62.82±1.56), (63.35±2.06), (64.12±1.76), (63.52±2.02) and (63.48±1.55)pg/ml.There were significant differences of ET-1 and vWF concentrations among different groups and time points (ET-1: F_group=32.160, P=0.012; F_time=21.180, P=0.023.vWF: F_group=73.110, P=0.001; F_time=46.180, P=0.002). The nerve fiber bundles was swelled with disordered arrangement and vacuolization 8 weeks after irradiation.Axon swell and atrophy, axons with myelin sheath layer plate separation were obtained.The rates of axon demyelination in the normal control group and model group were (1.35±0.79)% and (14.44±2.32)%, respectively.There was a statistically significant difference between the two groups (t=14.07, P<0.01).

Conclusions

The total 30 Gy dose of radiation on the head of rats can make stable radioactive optic nerve injury model.This model making method is simple, cheap and practical, which is worth further study.