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https://hdl.handle.net/2440/61184
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Type: | Journal article |
Title: | Lentivirus-mediated gene transfer of interleukin 10 to the ovine and human cornea |
Author: | Parker, D. Coster, D. Brereton, H. Hart, P. Koldej, R. Anson, D. Williams, K. |
Citation: | Clinical and Experimental Ophthalmology, 2010; 38(4):405-413 |
Publisher: | Blackwell Publishing Asia |
Issue Date: | 2010 |
ISSN: | 1442-6404 1442-9071 |
Statement of Responsibility: | Douglas G. Parker, Douglas J. Coster, Helen M. Brereton, Prue H. Hart, Rachel Koldej, Donald S. Anson and Keryn A. Williams |
Abstract: | <h4>Background</h4>Gene transfer to a donor cornea ex vivo can modulate corneal graft failure in experimental animal models. We compared a lentiviral vector (LV) carrying the transgene ovine interleukin 10 (IL10) with a comparable adenoviral vector (Ad) for its ability to transduce ovine and human corneas and to modulate ovine corneal allograft survival.<h4>Methods</h4>The LV carrying the ovine IL10 gene was used to transduce ovine and human corneas in vitro. LV-mediated gene expression in corneal endothelium was assessed by real-time quantitative reverse-transcriptase polymerase chain reaction, at varying doses and duration of transduction. The effect of ex vivo transduction of the donor cornea with LV-SV40-IL10 was assessed following orthotopic corneal transplantation in outbred sheep.<h4>Results</h4>Expression of IL10 mRNA in Ad-CMV-IL10-transduced ovine corneas was 10(3)-fold higher than in LV-SV40-IL10-transduced corneas (P < 0.0001), and 10(7)-fold higher than in non-transduced controls. IL10 was secreted rapidly from Ad-CMV-IL10-transduced, organ-cultured corneas, peaking at 13-15 days. IL10 secreted from LV-SV40-IL10-transduced corneas increased 20-fold compared with controls, but had not reached a plateau at 15 days. Gene expression driven by LV-SV40-IL10 varied with vector dose and transduction time, but was less than with Ad-CMV-IL10 at both mRNA and protein levels. Gene expression driven by LV-SV40-IL10 was faster in the human cornea than the ovine cornea. Corneal allograft survival was prolonged by a median of 7 days in the LV-SV40-IL10-treated recipients, compared with the control group (P = 0.026).<h4>Conclusion</h4>Although lentiviral vectors show some promise for corneal gene therapy, they are less efficient than adenoviral vectors. |
Keywords: | adenoviral vector corneal transplantation gene therapy lentiviral vector. |
Rights: | © 2010 The Authors. Journal compilation © 2010 Royal Australian and New Zealand College of Ophthalmologists |
DOI: | 10.1111/j.1442-9071.2010.02261.x |
Published version: | http://dx.doi.org/10.1111/j.1442-9071.2010.02261.x |
Appears in Collections: | Aurora harvest 5 Paediatrics publications |
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