[Neuroprotective effect of rAAV-mediated rhBDNF gene transfection on rabbit retina against acute high intraocular pressure].
OBJECTIVE
To investigate the neuroprotective effect of human brain-derived neurotrophic factor gene transfection into rabbit retina against acute high intraocular pressure (HIOP).


METHODS
Acute HIPO was induced in one eye of 24 white rabbits via saline perfusion into the anterior chamber (model group), and the contralateral eye without treatment served as the control group. In another 24 rabbits, 10 microl recombinant adeno-associated virus (rAAV) vector containing human BDNF gene (rAAV-BDNF) was injected into the vitreous body of one of the eyes 3 days before the operation for HIPO (BDNF group). At 1, 3, 7, and 14 days after HIOP model establishment, 6 eyes in each group were excised to observe the number of retinal ganglion cells (RGCs) and the thickness of the inner retina layer. For the eyes dissected on day 14, electroretinogram b (ERG-b) wave was detected 30 min before (baseline) and on days 1, 3, 7 and 14 after HIOP. Another 5 rabbits were used for ultrastructural observation of the RGCs using transmission electron microscopy, including 1 without treatment, 2 with unilateral HIOP and 2 with rAAV-BDNF transfection before HIOP.


RESULTS
The amplitude of ERG-b wave showed no significant difference between the 3 groups before HIOP (P>0.05). In HIOP model group and BDNF group, the amplitude decreased to the lowest at 1 day after HIOP and failed to recover the baseline level at 14 days (P<0.01); at the end of the observation, the amplitude was significantly higher in BDNF group than in the model group (P<0.01). Decreased number of RGCs and thickness of inner retina layer occurred in the model group, but these changes were milder in BDNF group (P<0.05, P<0.01). Electron microscopy revealed ultrastructural changes in the RGCs following acute HIOP, and transfection with rAAV-BDNF ameliorated these changes.


CONCLUSIONS
rAAV-BDNF transfection protects the retinal structure and improves the amplitude of ERG-b wave after acute high IOP suggesting its neuroprotective effects.
Department of Ophthalmology, Second Affiliated Hospital, Xi'an Jiaotong University College of Medicine, Xi'an, China. xajdwjm@163.com.
Jian-ming
JM
Wang
Nai-xue
NX
Sun
Na
N
Hui
Ya-zhi
YZ
Fan
Hai-xiao
HX
Feng
Shi-ping
SP
Zhao
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis / Q000235:genetics*; D000229:Dependovirus / Q000235:genetics* / Q000378:metabolism; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D009798:Ocular Hypertension / Q000150:complications / Q000628:therapy*; D011817:Rabbits; D012160:Retina / Q000473:pathology; D012164:Retinal Diseases / Q000209:etiology / Q000517:prevention & control*; D014162:Transfection
D019208:Brain-Derived Neurotrophic Factor