Date(s) - 12/13/2012
The corneal wound healing pathway involving the Transforming Growth Factor system has been extensively studied for their fibrotic role in cornea, skin, liver and kidney among other tissues. In this study, we have developed a gene therapy treatment to reduce corneal haze by targeting three critical scarring genes– Transforming Growth Factor ß1 (TGFB1), TGFß receptor (TGFBR2) and Connective Tissue Growth Factor (CTGF).
Starting with in vitro results and by using computational analysis, we generated two siRNA triple combinations – an “Effective” with optimal synergy and an “Ineffective” with poor synergy among its individual sequences. The efficient combination led to significant reduction in the steady state levels of the target growth factors and of the downstream mediators like Collagen-I and SMA and outperformed the ineffective combination. Employing ex vivo organ culture and in vivo animal testing, we were able to establish a method to deliver the triple combination using nanoparticles.
The result 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 skin.