title: 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.
authors.affiliation: The Cole Eye Institute, Cleveland Clinic, 9500 Euclid Ave., Cleveland, OH 44195, USA; LV Prasad Eye Institute, HERF, Hyderabad, AP, India.
authors.forename: Vivek
authors.initials: V
authors.lastname: Singh
authors.affiliation: Department of Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Ritika
authors.initials: R
authors.lastname: Jaini
authors.affiliation: The Cole Eye Institute, Cleveland Clinic, 9500 Euclid Ave., Cleveland, OH 44195, USA.
authors.forename: André A M
authors.initials: AA
authors.lastname: Torricelli
authors.affiliation: The Cole Eye Institute, Cleveland Clinic, 9500 Euclid Ave., Cleveland, OH 44195, USA.
authors.forename: Marcony R
authors.initials: MR
authors.lastname: Santhiago
authors.affiliation: Moran Eye Center, University of Utah, Salt Lake City, UT, USA.
authors.forename: Nirbhai
authors.initials: N
authors.lastname: Singh
authors.affiliation: Moran Eye Center, University of Utah, Salt Lake City, UT, USA.
authors.forename: Bala K
authors.initials: BK
authors.lastname: Ambati
authors.affiliation: The Cole Eye Institute, Cleveland Clinic, 9500 Euclid Ave., Cleveland, OH 44195, USA. Electronic address: wilsons4@ccf.org.
authors.forename: Steven E
authors.initials: SE
authors.lastname: Wilson
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism; D060527:Corneal Keratocytes / Q000166:cytology* / Q000378:metabolism; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D005822:Genetic Vectors / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D058628:Myofibroblasts / Q000166:cytology* / Q000378:metabolism; D018903:Photorefractive Keratectomy; D010957:Plasmids; D020574:Proto-Oncogene Proteins c-sis / Q000037:antagonists & inhibitors / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects*; D013234:Stem Cells / Q000166:cytology*; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: D000199:Actins; D020574:Proto-Oncogene Proteins c-sis; D016212:Transforming Growth Factor beta; C544013:alpha-smooth muscle actin, mouse; D049452:Green Fluorescent Proteins
keywords: bone marrow-derived cells; cornea; haze; immunocytochemistry; keratocytes; myofibroblasts; opacity; plateletderived growth factor; stroma; transforming growth factor beta