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U. Pleyer, N. Gong, K. Vogt, A. Fluegel, H. Volk, T. Ritter; Overexpression of Nerve Growth Factor in Corneal Transplants Improves Allograft Survival . Invest. Ophthalmol. Vis. Sci. 2005;46(13):4741.
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Purpose: To investigate the effect and mechanism of nerve growth factor (NGF) to promote allograft survival in experimental corneal transplantation. Methods: A total of 49 female Lewis rats received 3.5 mm corneal grafts of DA donors. Recombinant adenovirus vectors (E1/E3–deficient) expressing either NGF (AdNGF) or E. coli ß–Galactosidase (Adß–Gal) as control vector have been used. Recipients were randomly assigned to receive either (1) no therapy, (2) local gene transfer of NGF (1x108 pfu) or (3) a single i.p. injection of AdNGF (1x109 pfu in 500 µl of PBS) one day before transplantation. Local Adß–Gal gene transfer (1x108 pfu) or i.p. injection of Adß–Gal (1x109 pfu) one day before transplantation served as control. The survival rates were recorded and the immunoregulatory effect of this treatment was examined by analysing the expression of various cytokines and pro/anti–apoptotic genes using quantitative RT–PCR in the graft and draining lymph nodes (day 12 post transplantation). Results: Local AdNGF–gene transfer was effective in prolonging the mean survival time (MST) of corneal grafts (MST 16.8 +/– 1.4 days, n=16) as compared to untreated (MST 13.1 +/– 0.3 days; n=16; p=0.002) and local Adß–Gal gene transfer (13.3+/– 0.3 days, n=6; p=0.03). In contrast, systemic AdNGF gene transfer did not result in improved corneal graft survival (MST 15.2+/–1.0 days, n=5) as compared to systemic Adß–Gal gene transfer (13.2+/–0.3 days; n=6, p>0.05). Quantitative RT–PCR analysis of cornea explants (day 12 post transplant) revealed increased expression of the anti–apoptotic gene bag–1 and reduced expression of the pro–apoptotic gene bax in the AdNGF group compared to the control group. Moreover, mRNA–expression of IFN–g was profoundly reduced in draining lymph nodes of AdNGF treated animals but not in controls. Conclusions: Gene–based administration of NGF is a promising strategy to prolong allograft survival by local ex vivo transfer and is sufficient to both up–regulate intra–corneal cytoprotective molecules and to inhibit proinflammatory cytokine mRNA expression in the draining lymph nodes
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