Purpose: Transforming growth factor-β (TGF-β) is an important mediator of wound healing responses. In the eye, TGF-β activity has been implicated in causing corneal haze after laser surgery and subconjunctival scarring following glaucoma surgery. The purpose of the study was to determine whether small interference RNAs (siRNAs) targeting the type II receptor of TGF-β (TβRII) could be used to suppress the TGF-β action. Methods: TβRII specific siRNAs designed from the human gene sequence were transfected into cultured human corneal fibroblasts. The protein and transcript levels of the receptor were determined by immunofluorescence, western blotting, and real time PCR. Immunofluorescence and immunoblotting were carried out to examine fibronectin assembly. A wound closure assay was used to assess cell migration in in vitro fibroblast cultures. In addition, the in vivo effects of TβRII siRNA were evaluated in a mouse model of ocular inflammation and fibrosis generated by subconjunctival injection of phosphate buffered saline and latex beads. Mouse TβRII siRNA was introduced into experimental eyes. Cellularity on tissue sections was evaluated after staining with hematoxylin and eosin. Collagen deposition was visualized by picrosirius red staining.

Results: TβRII siRNAs abrogated the receptor transcript and protein expression in cultured corneal fibroblasts. The gene knockdown inhibited fibronectin assembly and retarded cell migration. In the mouse model, introduction of TβRII specific siRNA significantly reduced the inflammatory response and matrix deposition. Conclusions: TβRII specific siRNAs were efficacious both in vitro and in vivo in knocking down the TGF-β action. A direct application of siRNA into eyes to downregulate TβRII expression may provide a novel therapy for preventing ocular inflammation and scarring.