Neuroprotection of adenoassociated vira-mediated brain-derived neurotrophic factor on retinal ganglion cells in DBA/2J mice with glaucoma
10.3760/cma.j.issn.2095-0160.2011.04.007
- VernacularTitle:腺相关病毒介导的脑源性神经营养因子对DBA/2J小鼠视网膜神经节细胞的保护作用
- Author:
Chu-kai, HUANG
;
Ming-zhi, ZHANG
;
Li-fang, LIU
;
Ling-ping, CEN
;
Miao-miao, HAN
- Publication Type:Journal Article
- Keywords:
Glaucoma,Intraocular pressure,Brain-derived neurotrophic factor;
Retinal ganglion cells
- From:
Chinese Journal of Experimental Ophthalmology
2011;29(4):314-318
- CountryChina
- Language:Chinese
-
Abstract:
Background Deficiency of neurotrophic factor is associated with the damage of optic nerve in glaucoma.Reaserches showed that ectopically applied neurotrophic factor has a transient neuroprotective effect in glaucoma model,and the viral expression of adeno-associated neurotrophie factor may provide long-term supplementation of neurotrophic factor and neuroprotection in tissues.Objective The present study Was to investigate the neuroproteetive effect of adeno-associated viral(AAV)-mediated brain-derived neurotrophic factor (BDNF)on retinal ganglion cells(RGCs)in DBA/2J mice with experimental glaucoma. Methods 10 clean DBA/2J mice were administered intravitreal injection with 1 microliter of AAV-BDNF-GFP in the left eyes at the age of 6 months,and the right eyes were injected with the same volume of saline solution as control.Intraocular pressure (IOP)was measured with Tonolab in the mice every month.Retinas were obtained after 3 months for the investigation of GFP expression in RGCs using fluorescence microscopy.Immunohistochemistry Was performed by applying TUJ1 and Cy3 antibodies to identify surviving RGCs. Results The IOP of DBA/2J mice were 11.90 mmHg and 11.40 mmHg in the right eyes and left eyes,respectively,at 4 months.The IOP of DBA/2J mice began to rise at 5 months and reached its peak in 8 month-old mice.There was no statistically significant difference in IOPs between the right eyes and the left eyes from 4 month-through 9 month-old mice(t=-1.78-0.61,P=0.11-0.90).Three months after intrlavitreal injection of AAV-BDNF-GFP,GFP was positively expressed in RGCs of retinas with the expression rate of 46.33%±8.08%.The over-expression of BDNF led to more RGCs survival than the control eyes (3168.13±1319.33/mm2 vs 2024.81±796.38/mm2,t=2.75,P=0.02). Conclusion These data suggest that BDNF can exert a protective effect in DBA/2J glaucoma mice.