title: Losartan Attenuates Scar Formation in Filtering Bleb After Trabeculectomy.
abstract: To examine the effects of losartan on scar formation after trabeculectomy and on fibrotic changes of human Tenon's fibroblasts (HTFs).
  
  
  
  Trabeculectomy was performed on New Zealand rabbits. They were randomized to receive one of the following treatments: 0.9% normal saline, mitomycin-C, or one of the three doses of losartan. Bleb morphology, IOP, and histopathology examination were performed. Primary cultured HTFs were treated with losartan or vehicle, with or without angiotensin II (Ang II). Cell proliferation was assessed by Cell Counting Kit-8 assay, and cell migration was detected by scratch wound and transwell assay. Transdifferentiation was evaluated through the expression of α-smooth muscle actin (α-SMA) by immunofluorescence, real-time PCR, and Western blot. The expression of fibronectin (FN) was evaluated by real-time PCR and Western blot.
  
  
  
  An amount of 5 mg/mL of losartan subconjunctival injection significantly decreased IOP postoperatively and attenuated wound healing of the filtering bleb in the rabbit model. Immunostaining results showed less myofibroblast and collagen deposition around the bleb area in the losartan-treated eyes. Losartan (10-5 M) in vitro significantly attenuated Ang II's stimulatory effects on proliferation and migration of HTFs. Expressions of α-SMA and FN in these cells were also decreased by losartan pretreatment.
  
  
  
  Losartan attenuates scar formation of filtering bleb after trabeculectomy likely via decreasing proliferation, migration, transdifferentiation, and extracellular matrix deposition of Tenon's fibroblasts. These results indicate that losartan may be an effective therapeutic agent in preventing bleb scar formation and in improving surgical outcome after trabeculectomy.
authors.affiliation: Department of Ophthalmology, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Huimin
authors.initials: H
authors.lastname: Shi
authors.affiliation: Department of Ophthalmology, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Huiying
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Ophthalmology, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Shuhao
authors.initials: S
authors.lastname: Fu
authors.affiliation: Department of Ophthalmology, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Kang
authors.initials: K
authors.lastname: Xu
authors.affiliation: Department of Ophthalmology, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Ophthalmology, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Yiqin
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Department of Ophthalmology, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Ye
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage; D000818:Animals; D015153:Blotting, Western; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D002921:Cicatrix / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology; D004195:Disease Models, Animal; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D005901:Glaucoma / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D006801:Humans; D007429:Intraocular Pressure; D019808:Losartan / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology; D012313:RNA / Q000235:genetics; D011817:Rabbits; D060888:Real-Time Polymerase Chain Reaction; D058475:Tenon Capsule / Q000378:metabolism / Q000473:pathology; D014130:Trabeculectomy / Q000009:adverse effects*
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D047228:Angiotensin II Type 1 Receptor Blockers; D012313:RNA; D019808:Losartan