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W-C Wu, C-C Lai, S-L Chen, X Xiao, T-L Chen, RJ F Tsai, S-W Kuo, Y-P Tsao; Rescue Of Photorecetors From Retinal Detachment-induced Damage By Adeno-associated Virus Vector Expressing Glial Cell Line-derived Neurotrophic Factor . Invest. Ophthalmol. Vis. Sci. 2002;43(13):650.
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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 retinal detachment (RD) induced photoreceptor damage by ways of gene delivery. Methods: Gene delivery to photoreceptors was achieved by subretinal injection of recombinant AAV expressing GDNF (rAAV-GDNF) in the right eyes and AAV expressing E. coli lacZ (rAAV-lacZ) in the left eyes of Lewis rats. RD in bilateral eyes was induced with subretinal injection of high-density vitreous substitute in the temporal retina 3 weeks after gene delivery. The synthesis and accumulation of GDNF within retina was monitored 3 weeks after RD by immunohistochemistry and enzyme-linked immunosorbent assay (ELISA)espectively. The rescue of photoreceptors was evaluated by monitoring the preservation of the thickness of photoreceptor outer segment (OS) and outer nuclear layer (ONL). Apoptosis of photoreceptors was studied using the TdT-dUTP terminal nick-end labeling (TUNEL) method 2 days after RD. Müller cell activity was checked using the immunohistochemistry with glial fibrillary acidic protein (GFAP) antibody. Results: The gene delivery was demonstrated by immunohistochemistry study. High levels of neurotrophic factors were produced in retina by ELISA study. Photoreceptor OS degeneration and the gradual shortening of the ONL were noted after RD in all the eyes. However, GDNF-treated eyes retained longer OS than controlled eyes 7 days (p=0.012) and 28 days (p=0.008) after RD. ONL was also longer in GDNF-treated eyes than in controlled eyes 7 days (p=0.012) and 28 days (p=0.008) after RD. GDNF-treated eyes had statistically less apoptotic cells than control eyes in photoreceptor layer (p=0.043). Müller cell activity was less prominent in GDNF-treated group, indicating less scar-formation activity. Conclusion: GDNF is a potential factor that can protect photoreceptors from degeneration. GDNF gene therapy may be a valuable adjuvant to current treatments in certain complicated forms of retinal detachment.
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