Synergistic Triple Combination of siRNAs to Knockdown Key Growth Factors and Receptors that Regulate Corneal Haze in Rabbits

Date(s) - 10/29/2013
8:30 am

Sriniwas Sriram, PhD Candidate

The Transforming Growth Factor β1 (TGFβ1), TGFβ receptor (TGFβR2) and Connective Tissue Growth Factor (CTGF) are key regulators of fibrosis in the cornea and in other tissues, including liver, skin and kidney.  In this study, an anti-fibrotic drug targeting these three critical scarring genes was developed using a synergistic combination of siRNAs, and its effect on downstream scarring genes, Collagen-I (Col-I) and alpha smooth muscle actin (SMA) was assessed in rabbit corneal fibroblasts (RbCFs). The efficacy of this synergistic triple siRNA combination in reducing corneal scarring (haze) in excimer laser ablated rabbits was also tested.

This work also aimed to develop and characterize scar formation in an ex vivo corneal organ culture model following laser ablation. The therapeutic potential of the model was evaluated by delivering the previously optimized synergistic triple siRNA combination to the cornea using a nanoparticle delivery system.

The results from this study paves the way towards developing a multi target approach for the reduction of corneal haze and perhaps of other scarring processes affecting the body.