TGFβ and PDGF-B signaling blockade inhibits myofibroblast development from both bone marrow-derived and keratocyte-derived precursor cells in vivo

Abstract

Myofibroblasts, the primary cells associated with corneal stromal haze (opacity), can be derived from both cornea-derived and bone marrow-derived precursor cells. In the present study, the role of TGFβ or PDGF blockage on bone marrow-derived myofibroblast development was investigated using a green fluorescent protein (GFP) chimeric bone marrow mouse model and plasmid vectors that blocked TGFβ or PDGF signaling. At the peak of corneal haze one month after irregular phototherapeutic keratectomy the central stroma had significantly less alpha-smooth muscle actin (α-SMA)-positive cells derived from GFP+ bone marrow-derived cells or GFP- keratocyte/corneal fibroblast-derived cells when corneas were treated with the TGFβ blocking vector pGFPC1.TGFRBKDEL or the PDGF blocking vector pCMV.PDGFRB.23KDEL compared with the corresponding empty vector treated or untreated control groups. In individual animals, 30-60% of myofibroblasts were derived from bone marrow-derived precursor cells and 40-70% of myofibroblasts were derived from keratocyte-derived precursor cells. TGFβ and PDGF regulate corneal myofibroblast development from bone marrow-derived precursor cells and keratocyte/corneal fibroblast-derived precursor cells.

Keywords: bone marrow-derived cells; cornea; haze; immunocytochemistry; keratocytes; myofibroblasts; opacity; plateletderived growth factor; stroma; transforming growth factor beta.