title: A complement receptor C5a antagonist regulates epithelial to mesenchymal transition and crystallin expression after lens cataract surgery in mice.
abstract: OBJECTIVE
  To evaluate the effects of complement employing a mouse model for secondary cataract.
  
  
  METHODS
  The role of complement receptor C5a (CD88) was evaluated after cataract surgery in mice. An antagonist specific to C5a receptor was administered intraperitoneally to mice. Epithelial to mesenchymal transition (EMT) was evaluated by alpha-smooth muscle actin (α-SMA) staining and proliferation by bromodeoxyuridine (5-bromo-2'-deoxyuridine, BrdU) incorporation. Gene expression patterns was examined by microarray analysis and quantitative polymerase chain reaction (QPCR).
  
  
  RESULTS
  We found that administration of a C5aR antagonist in C57BL/6J mice decreases EMT, as evidenced by α-SMA expression, and cell proliferation. Gene expression by microarray analysis reveals discreet steps of gene regulation in the two major stages that of EMT and lens fiber differentiation in vivo. A hallmark of the microarray analysis is that the antagonist seems to be a novel stage-specific regulator of crystallin genes. At week two, which is marked by lens fiber differentiation genes encoding 12 crystallins and 3 lens-specific structural proteins were severely down-regulated.
  
  
  CONCLUSIONS
  These results suggest a possible therapeutic role of an antagonist to C5aR in preventing secondary cataracts after surgery. Also these results suggest that crystallin gene expression can be regulated by pro-inflammatory events in the eye.
authors.affiliation: Department of Biology and Center for Tissue Regeneration and Engineering at Dayton, University of Dayton, Dayton, OH 45469-2320, USA.
authors.forename: Rinako
authors.initials: R
authors.lastname: Suetsugu-Maki
authors.forename: Nobuyasu
authors.initials: N
authors.lastname: Maki
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Fox
authors.forename: Kenta
authors.initials: K
authors.lastname: Nakamura
authors.forename: Richard
authors.initials: R
authors.lastname: Cowper Solari
authors.forename: Craig R
authors.initials: CR
authors.lastname: Tomlinson
authors.forename: Hongchang
authors.initials: H
authors.lastname: Qu
authors.forename: John D
authors.initials: JD
authors.lastname: Lambris
authors.forename: Panagiotis A
authors.initials: PA
authors.lastname: Tsonis
mesh_terms: D000199:Actins / Q000032:analysis; D000818:Animals; D001973:Bromodeoxyuridine / Q000032:analysis; D002386:Cataract / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015936:Complement C5a / Q000378:metabolism; D003459:Crystallins / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005260:Female; D005786:Gene Expression Regulation; D007274:Injections, Intraperitoneal; D007908:Lens, Crystalline / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D046228:Microarray Analysis; D013508:Ophthalmologic Surgical Procedures / Q000009:adverse effects; D010456:Peptides, Cyclic / Q000008:administration & dosage* / Q000627:therapeutic use; D016133:Polymerase Chain Reaction; D044087:Receptor, Anaphylatoxin C5a / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: C438957:AcPhe(ornithine-Pro-cyclohexylamine-Trp-Arg); D000199:Actins; D003459:Crystallins; D010456:Peptides, Cyclic; D044087:Receptor, Anaphylatoxin C5a; C544013:alpha-smooth muscle actin, mouse; D015936:Complement C5a; D001973:Bromodeoxyuridine