Reduction of Corneal Scarring Following Blast and Burn Injuries to Cornea Using siRNAs Targeting TGFb and CTGF

摘要

Blast and burn injuries to the eye caused by explosions during combat operations or terrorist attacks are devastating injuries, and in eyes that can be saved, the major causes of vision impairment are excessive corneal scarring and neovascularization. Unfortunately, no approved drugs have been shown to improve vision outcome in eyes with these types of corneal injuries. However, decades of clinical experience and laboratory research have shown that the key to improving vision outcome is to improve the quality of corneal wound healing.(1), (2), (3) Our overall objective was to develop new drugs that use the emerging technology of RNA-interference (RNAi) to reduce vision impairment following corneal injuries by reducing expression of genes that stimulate formation of corneal scar (corneal haze).(4) We reported previously that corneal scarring is primarily up-regulated by the actions of transforming growth factor beta (TGFb), which stimulates corneal cells by binding to the TGFb type II receptor (TGFbRII) and inducing expression of connective tissue growth factor (CTGF).(5) CTGF then directly up-regulates synthesis of collagen scar and induces transformation of fibroblasts into myofibroblasts. Our approach was to design and test small interfering RNAs (siRNA) that will selectively reduce the level of expression of these three key proteins that stimulate corneal scar formation, and thereby, reduce vision loss.