Decorin Biology, Expression, Function and Therapy in the Cornea

R.      R. Mohan; J.      C.K. Tovey; R.      Gupta; A.      Sharma; A.      Tandon

doi:10.2174/156652411794859241

Abstract

Decorin is a small leucine-rich proteoglycan (SLRP) that plays a vital role in many important cellular processes in several tissues including the cornea. A normal constituent of the corneal stroma, decorin is also found in the majority of connective tissues and is related structurally to other small proteoglycans. It interacts with various growth factors such as epidermal growth factor (EGF) and transforming growth factor beta (TGFβ) to regulate processes like collagen fibrillogenesis, extracellular matrix (ECM) compilation, and cell-cycle progression. Studies have linked decorin dysregulation to delayed tissue healing in patients with various diseases including cancer. In the cornea, decorin is involved in the regulation of transparency, a key function for normal vision. It has been reported that mutations in the decorin gene are associated with congenital stromal dystrophy, a disease that leads to corneal opacity and visual abnormalities. Decorin also antagonizes TGFβ in the cornea, a central regulatory cytokine in corneal wound healing. Following corneal injury, increased TGFβ levels induce keratocyte transdifferentiation to myofibroblasts and, subsequently, fibrosis (scarring) in the cornea. We recently reported that decorin overexpression in corneal fibroblasts blocks TGFβ-driven myofibroblast transformation and fibrosis development in the cornea in vitro suggesting that decorin gene therapy can be used for the treatment of corneal scarring in vivo.

Keywords: Cornea, corneal haze/scarring, decorin, gene therapy, TGF-beta, fibrosis, collagen fibrillogenesis, neovascularization, Ehlers Danlos syndrome, proangiogenic effects, congenital stromal dystrophy, angiogenesis, proteoglycans, translation, lysosomal proteolysis