VRP09 Reduction of Corneal Scarring Following Blast and Burn Injuries to Cornea Using siRNAs Targeting TGFb and CTGF
Abstract
Blast and burn injuries to the eye caused by explosions during combat or terrorist attacks are devastating injuries, which typically impair vision by excessive corneal scarring. Our overall goal is to develop a topical therapy that will reduce corneal scarring by selectively reducing expression of TGFb, TGFb receptor-II (RGFBRII), and CTGF genes which cause scarring using the newly discovered effects of small interfering RNAs (siRNA). In the second year o of the project we tested and identified one triple combination of siRNAs that generated a true synergistic knockdown of the expression of collagen gene by 97% and of alpha smooth muscle actin (aSMA) by 94% in RCF cultures without compromising the viability of the RCF. We then developed nanoparticle formulations containing this triple combination of siRNAs and showed that the nanoparticles effectively delivered the siRNAs to all layers of rabbit corneas using ex vivo rabbit globes. We performed a pilot test of this formulation in vivo using the rabbit corneal excimer laser ablation model that simulates blast injuries. The knockdown of collagen and aSMA was very effective in two of three rabbits. We are optimizing the delivery further and will perform and full test in rabbits in the 6-month no cost extension that was approved in late 2012.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2012
- Accession Number
- ADA602605
Entities
People
- Gregory Schultz
Organizations
- University of Florida