Journal
MOLECULAR THERAPY
Volume 18, Issue 11, Pages 1917-1926Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/mt.2010.167
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Funding
- Ellison Foundation
- National Institutes of Health/National Eye Institute [EY014991, EY013887]
- Virginia B Smith Trust
- Lions Eye Foundation and Research to Prevent Blindness
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Peptide for ocular delivery (POD) is a novel cationic cell-penetrating peptide (CPP) which, when conjugated with polyethylene glycol (PEG-POD), can deliver plasmid DNA to the retinal pigment epithelium (RPE) of adult murine retina. PEG-POD nanoparticles containing an expression cassette for glial cell line-derived neurotrophic factor (PEG-POD similar to GDNF) were investigated for their ability to inhibit light-induced photoreceptor apoptosis. PEG-POD similar to GDNF, control nanoparticles, or buffer were injected into the subretinal space of adult murine retina and retinal degeneration induced by blue light. Animals injected with PEG-POD similar to GDNF showed a significant reduction (3.9-7.7 fold) in apoptosis relative to control-injected animals. The thickness of the outer nuclear layer (ONL) of the superior retina of PEG-POD similar to GDNF-injected eyes was significantly greater (23.6-39.3%) than control-injected retina 14 days post-light treatment. PEG-POD similar to GDNF-injected eyes showed a 27-39% greater functional response relative to controls, as measured by electroretinogram (ERG) 7 days post-light treatment. This is one of only two studies demonstrating histological and functional rescue of a mouse model of retinal degeneration following nonviral administration of a transgene into adult retina. Although rescue is short lived for clinical application, this study represents an important step in the development of nonviral gene therapy for retinal diseases.
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