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W. Wu, C. Lai, S. Chen, M. Sun, X. Xiao, T. Chen, R.J. Tsai, S. Kuo, Y. Tsao; GDNF Gene Therapy Attenuates Injuries after Retinal Ischemia in Rats . Invest. Ophthalmol. Vis. Sci. 2003;44(13):3577.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To examine the protective effect of glial cell line-derived neurotrophic factor (GDNF) on ischemia-reperfusion injury by using gene delivery. Methods: Gene delivery to retinal ganglion cells (RGCs) was achieved by intravitreal injection of recombinant adeno-associated virus expressing GDNF (rAAV-GDNF) in the right eyes and AAV expressing E. coli LacZ (rAAV-LacZ) in the left eyes of Sprague-Dawley rats. Ischemia-reperfusion injury was conducted 3 weeks after gene delivery. The synthesis and accumulation of GDNF within retina was monitored 3 weeks after gene delivery by immunohistochemistry and enzyme-linked immunosorbent assay (ELISA) respectively. The neuroprotective effects were evaluated by monitoring the preservation of the thickness of inner retina, RGCs counting. Functional study was performed using eletroretinogram (ERG). Apoptosis of retina was studied using the TdT-dUTP terminal nick-end labeling (TUNEL) method. Results: Gene delivery was demonstrated by immunohistochemistry study. The results of ELISA confirmed that high levels of neurotrophic factors were produced in retinas. Thinning of the inner retina and decreased number of RGCs were noted after ischemia in all the eyes. However, the thickness of inner retina and the numbers of RGCs were better preserved in rAAV-GDNF treated eyes than rAAV-LacZ treated eyes 7 days after reperfusion (p=0.038 and p=0.003 respectively). rAAV-GDNF treated eyes retained larger b-wave amplitude than rAAV-LacZ treated eyes 7 days after reperfusion (p=0.003). GDNF-treated eyes had statistically less apoptotic cells than control eyes in RGC layer (P=0.021). Conclusions: GDNF is a potential factor that can protect retina from ischemia-reperfusion injury. GDNF exerts its protective action by preventing the apoptosis of retinal cells after ischemia. GDNF gene therapy may be a valuable tool to retinal ischemia.
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