¡¡¡¡DISCUSSION

¡¡¡¡Gene therapy is believed to have great potential for treatment of diseases in eyes. It was reported that brain derived neurotrophic factor (BDNF) could improve the survival of retina ganglion cells when the optic nerve was injured[4,5]. However, the clinical application of BDNF is limited because BDNF, a macromolecular protein, is unable to pass the bloodª²retina barrier. Therefore, researchers have made efforts to introduce BDNF gene into oculi using different gene vectors, include adenoª²associated virus (AAV), adenovirus, retrovirus, among others [6ª²9].

¡¡¡¡AAV can be integrated into the human 19th chromosome long arm and can transfect proliferation cells and nonproliferation cells. AAV does not result in disease, and, compared with other vectors, AAV can make the target gene express stably over the long term. Therefore, it is necessary to investigate whether the recombinant AAV (rAAV) is an effective vector for transferring targeting genes for gene therapy of retinal and optic nerve diseases.

¡¡¡¡In this study, we select GFP gene as a target gene since GFP, an irradiated protein, can be easily detected by showing green fluorescence after irradiation with blue or ultraviolet light. We found that fluorescent spots in the cytoplasm of retinal cells could be observed three days after intravitreal injection of rAAVª²gfp, and fluorescence intensity significantly on day 7 and 14 postª²infection. These results confirm that rAAV is an ideal vector that can effectively transfer the GFP gene into the rabbit retina, which suggesting that rAAV can be used for transferring a target gene for gene therapy of diseases in eyes.

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¡¡¡¡2 Sarra GM, Stephens C, Schlichtenbrede FC, Bainbridge JW, Thrasher AJ, Luthert PJ, Ali RR. Kinetics of transgene expression in mouse retina following subª²retinal injection of recombinant adenoª²associated virus. Vision Res 2002; 42(4): 541ª²549

¡¡¡¡3 Shan Q, Zhang J, Ren H, Wang DL, Yi HT, Wu XB, Qian HW. Experimental study on adenoª²associated virusª²mediated genetransfer into the rabbit retina. Rec Adv Ophthalmol2001;21(4): 225ª²227

¡¡¡¡4 Ma YT, Hsieh T, Forbes ME, Johnson JE, Frost DO. BDNF injected into the superior colliculus reduces developmental retinal ganglion cell death. J Neurosci1998;18(6): 2097ª²2107

¡¡¡¡5 Xie YB, Niu YJ, Yuan CY, Yang Y, Zhou WY, Yu XT. Effects of brainª²derived neurotrophic factor on the expression of caspaseª²2 and caspaseª²3 and cell apoptosis in retinal ischemia/reperfusion injury. Int J
Ophthalmol(Guoji Yanke Zazhi)2007;7(5):1217ª²1222

¡¡¡¡6 Bennett J, Maguire AM, Cideciyan AV, Schnell M, Glover E, Anand V, Aleman TS, Chirmule N, Gupta AR, Huang Y, Gao GP, Nyberg WC, Tazelaar J, Hughes J, Wilson JM, Jacobson SG. Stable transgene expression in rod photoreceptors after recombinant adenoª²associated virusª²mediated gene transfer to monkey retina. Proc Natl Acad Sci USA 1999;96(17):9920ª²9925

¡¡¡¡7 Di Polo A, Aigner LJ, Dunn RJ, Bray GM, Aguayo AJ. Prolonged delivery of brainª²derived neurotrophic factor by adenovirusª²infected M ller cells temporarily rescues injured retinal ganglion cells. Proc Natl Acad
Sci U S A1998;95(7):3978ª²3983

¡¡¡¡8 Spencer B, Agarwala S, Miskulin M, Smith M, Brandt CR. Herpes simplex virusª²mediated gene delivery to the rodent visual system. Invest Ophthalmol Vis Sci 2000;41(6):1392ª²1401

¡¡¡¡9 Grant CA, Ponnazhagan S, Wang XS, Srivastava A, Li T. Evaluation of recombinant adenoª²associated virus as a gene transfer vector for the retina. Curr Eye Res1997;16(9): 949ª²956

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