1. Investigating the Global Dispersal of Chickens in Prehistory Using Ancient Mitochondrial DNA Signatures.
- Author
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Storey, Alice A., Stephen Athens, J., Bryant, David, Carson, Mike, Emery, Kitty, DeFrance, Susan, Higham, Charles, Huynen, Leon, Intoh, Michiko, Jones, Sharyn, Kirch, Patrick V., Ladefoged, Thegn, McCoy, Patrick, Morales-Muñiz, Arturo, Quiroz, Daniel, Reitz, Elizabeth, Robins, Judith, Walter, Richard, and Matisoo-Smith, Elizabeth
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MITOCHONDRIAL DNA , *NEOVASCULARIZATION , *EYE diseases , *BLINDNESS , *CELL proliferation , *LIPIDS - Abstract
Retinal neovascularization is a critical component in the pathogenesis of common ocular disorders that cause blindness, and treatment options are limited. We evaluated the therapeutic effect of a DNA enzyme targeting c-jun mRNA in mice with preexisting retinal neovascularization. A single injection of Dz13 in a lipid formulation containing N-[1-(2,3-dioleoyloxy)propyl]- N,N,N-trimethylammonium methyl-sulfate and 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine inhibited c-Jun expression and reduced retinal microvascular density. The DNAzyme inhibited retinal microvascular density as effectively as VEGF-A antibodies. Comparative microarray and gene expression analysis determined that Dz13 suppressed not only c-jun but a range of growth factors and matrix-degrading enzymes. Dz13 in this formulation inhibited microvascular endothelial cell proliferation, migration and tubule formation in vitro. Moreover, animals treated with Dz13 sensed the top of the cage in a modified forepaw reach model, unlike mice given a DNAzyme with scrambled RNA-binding arms that did not affect c-Jun expression. These findings demonstrate reduction of microvascular density and improvement in forepaw reach in mice administered catalytic DNA. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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