title: A p38 MAPK inhibitor improves outcome after glaucoma filtration surgery.
abstract: OBJECTIVE
  The aim of this study is to explore the effects of SB 202190, a highly selective p38 MAPK inhibitor, on bleb survival following glaucoma filtering surgery.
  
  
  METHODS
  Human Tenon's fibroblasts were treated with SB 202190 (0 to 100 μM) to determine IC50, and cell proliferation and migration. Twenty rabbits were divided into 4 groups (G1-G4): G1 animals received only a trabeculectomy. G2-G4 animals had trabeculectomy plus one of the following subconjunctival adjuvants, given intraoperatively and postoperatively: G2=sham, G3=20 μM SB 202190, and G4=50 μM SB 202190. The blebs were assessed using the Indiana Bleb Appearance Grading Scale. The intraocular pressure (IOP) was expressed as the right to left eye ratio (R/L ratio). For morphometric bleb analysis the JMicrovision software was used.
  
  
  RESULTS
  SB 202190 inhibits human Tenon's fibroblasts proliferation and migration in vitro (IC50=17.2 μM). In vivo subconjunctival application of SB 202190 after glaucoma filtration surgery significantly increases bleb height, bleb extension, and bleb survival time compared with the control. In all groups, the IOP ratio correlates with the fibrotic process. G3 shows a significantly reduced IOP ratio at day 14 compared with the control. Analysis of the bleb histology shows that G3 has a significant smaller fibrosis area compared with G1 and G2. Application of the highest dose (50 μM SB 202190) is associated with hyphema in 2 of 5 animals (40%).
  
  
  CONCLUSIONS
  Application of SB 202190 significantly improves bleb characteristics and IOP control after filtering glaucoma surgery in a rabbit model.
authors.affiliation: *Department of Ophthalmology, University of Luebeck, Luebeck, Germany †Department of Ophthalmology, Fayoum University, Fayoum, Egypt.
authors.forename: Khaled
authors.initials: K
authors.lastname: Nassar
authors.forename: Aysegul
authors.initials: A
authors.lastname: Tura
authors.forename: Julia
authors.initials: J
authors.lastname: Lüke
authors.forename: Matthias
authors.initials: M
authors.lastname: Lüke
authors.forename: Salvatore
authors.initials: S
authors.lastname: Grisanti
authors.forename: Swaantje
authors.initials: S
authors.lastname: Grisanti
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D005347:Fibroblasts / Q000473:pathology; D005355:Fibrosis / Q000517:prevention & control; D005901:Glaucoma / Q000473:pathology / Q000601:surgery*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D007429:Intraocular Pressure / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology*; D011817:Rabbits; D058475:Tenon Capsule / Q000166:cytology; D014065:Tonometry, Ocular; D014130:Trabeculectomy; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*
chemical_list: D004791:Enzyme Inhibitors; D007093:Imidazoles; D011725:Pyridines; D048051:p38 Mitogen-Activated Protein Kinases; C090942:4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole