title: Different fibroblast subpopulations of the eye: a therapeutic target to prevent postoperative fibrosis in glaucoma therapy.
abstract: The aim of this study is the characterization of fibroblasts mainly responsible for fibrosis processes associated with trabeculectomy or microstent implantation for glaucoma therapy. Therefore we isolated human primary fibroblasts from choroidea, sclera, Tenon capsule, and orbital fat tissues. These fibroblast subpopulations were analysed in vitro for expression of the extracellular matrix components which are responsible for postoperative scarring in glaucoma therapy. For scarring the proteins of the collagen family are predominant and so we focused on the expression of collagen I, collagen III and collagen VI in every fibroblast subpopulation. Also, the extracellular matrix protein fibronectin which crosslinks collagen fibres or other extracellular matrix components and cell surfaces, was analyzed. Collagen I, III and VI were prominent in every fibroblast subpopulation. The highest amounts of collagen III were found in hCF and hOF, whereas the signal in hSF and hTF was negligible. Additionally, there is a link between scarring processes and proliferating potential of fibroblasts, in case of microstent implantation triggered through the infiltration of inflammatory cells. Thus we analyzed fibroblast subpopulations for the presence of TGF-β1 which is one of the most important cytokines involved in proliferation processes. TGF-β1 was prominent in all fibroblast subpopulations with lowest expression in hCF cultures. To prevent postoperative fibroblast proliferation we analyzed in vitro the proliferation-inhibitors paclitaxel and mitomycin C which are potential candidates in drug eluting drainage systems on ocular fibroblast subpopulations. These inhibitors arrest fibroblast proliferation and viability, being, however, not very specific and have a cytotoxic potential also on healthy tissues surrounding the microstent outflow area. Significant differences in protein synthesis of fibroblasts subpopulations which could be specific targets for inhibition may help to find out fibroblast specific inhibitors to prevent postoperative scarring and could prevent patients from secondary surgery after microstent implantation.
authors.affiliation: Department of Ophthalmology, University of Rostock, Doberaner Straße 140, D-18057 Rostock, Germany. thomas.stahnke@med.uni-rostock.de
authors.forename: Thomas
authors.initials: T
authors.lastname: Stahnke
authors.forename: Marian
authors.initials: M
authors.lastname: Löbler
authors.forename: Christian
authors.initials: C
authors.lastname: Kastner
authors.forename: Oliver
authors.initials: O
authors.lastname: Stachs
authors.forename: Andreas
authors.initials: A
authors.lastname: Wree
authors.forename: Katrin
authors.initials: K
authors.lastname: Sternberg
authors.forename: Klaus-Peter
authors.initials: KP
authors.lastname: Schmitz
authors.forename: Rudolf
authors.initials: R
authors.lastname: Guthoff
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D018929:Cell Culture Techniques; D049109:Cell Proliferation; D002829:Choroid / Q000166:cytology; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism; D005355:Fibrosis / Q000517:prevention & control; D019084:Fluorescent Antibody Technique, Indirect; D005901:Glaucoma / Q000473:pathology / Q000601:surgery*; D020327:Glaucoma Drainage Implants; D006801:Humans; D015151:Immunoblotting; D016685:Mitomycin / Q000494:pharmacology; D017239:Paclitaxel / Q000494:pharmacology; D012590:Sclera / Q000166:cytology; D058475:Tenon Capsule / Q000166:cytology; D014129:Trabecular Meshwork / Q000473:pathology; D014130:Trabeculectomy; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D016326:Extracellular Matrix Proteins; D053773:Transforming Growth Factor beta1; D016685:Mitomycin; D017239:Paclitaxel