Feasibility of Direct Vitrectomy-Sparing Subretinal Injection for Gene Delivery in Large Animals
Language English Country England, Great Britain Media print-electronic
Document type Journal Article
- Keywords
- Subretinal injection, large animal, non-viral gene vector, pars plana vitrectomy, safety,
- MeSH
- Genetic Therapy * methods MeSH
- Genetic Vectors * administration & dosage MeSH
- Injections, Intraocular MeSH
- Swine, Miniature * MeSH
- Disease Models, Animal MeSH
- Pilot Projects MeSH
- Plasmids administration & dosage MeSH
- Swine MeSH
- Retina MeSH
- Feasibility Studies * MeSH
- Gene Transfer Techniques * MeSH
- Vitrectomy * methods MeSH
- Green Fluorescent Proteins genetics MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Green Fluorescent Proteins MeSH
PURPOSE: To assess the safety and feasibility of direct vitrectomy-sparing subretinal injection for gene delivery in a large animal model. METHODS: The experimental Liběchov minipigs were used for subretinal delivery of a plasmid DNA vector (pS/MAR-CMV-copGFP) with cytomegalovirus (CMV) promoter, green fluorescent protein (GFP) reporter (copGFP) and a scaffold/matrix attachment region (S/MAR) sequence. The eyes were randomized to subretinal injection of the vector following pars plana vitrectomy (control group) or a direct injection without prior vitrectomy surgery (experimental group). Intra- and post-operative observations up to 30 days after surgery were compared. RESULTS: Six eyes of three mini-pigs underwent surgery for delivery into the subretinal space. Two eyes in the control group were operated with a classical approach (lens-sparing vitrectomy and posterior hyaloid detachment). The other four eyes in the experimental group were injected directly with a subretinal cannula without vitrectomy surgery. No adverse events, such as endophthalmitis, retinal detachment and intraocular pressure elevation were observed post-operatively. The eyes in the experimental group had both shorter surgical time and recovery while achieving the same surgical goal. CONCLUSIONS: This pilot study demonstrates that successful subretinal delivery of gene therapy vectors is achievable using a direct injection without prior vitrectomy surgery.
Department of Ophthalmology Oslo University Hospital Kirkeveien 166 Oslo Norway
German Cancer Research Center Heidelberg Germany
Karl Landsteiner Institute for Retinal Research and Imaging Vienna Austria
Moorfields Eye Hospital NHS Foundation Trust London United Kingdom
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