title: An ophthalmic solution of a peroxisome proliferator-activated receptor gamma agonist prevents corneal inflammation in a rat alkali burn model.
abstract: OBJECTIVE
  We clarified the effects of an ophthalmic solution of a peroxisome proliferator-activated receptor gamma (PPARγ) agonist on corneal inflammation and wound healing after alkali burn injury in rats.
  
  
  METHODS
  After alkali exposure, either an ophthalmic solution with 0.1% pioglitazone hydrochloride (the PPARγ group) or vehicle (the vehicle group) was topically applied to the cornea until day 14. Histological, immunohistochemical, and real-time reverse transcription polymerase chain reaction analysis were performed.
  
  
  RESULTS
  After alkali injury, PPARγ expression increased, with the infiltration of many inflammatory cells. The infiltration of neutrophils and macrophages started from the corneal limbus within 6 h, and developed in the corneal center by day 7, with associated neovascularization. The accumulation of α-smooth muscle actin-positive myofibroblasts and the deposition of type III collagen were noted on day 14. The histological changes were suppressed significantly by treatment with the ophthalmic solution of the PPARγ agonist. In addition, the number of infiltrating M2 macrophages in the cornea was increased by PPARγ agonist treatment. In real-time reverse transcription polymerase chain reaction analysis, the messenger ribonucleic acid expression levels of interleukin-1β (IL-1β), IL-6, IL-8, monocyte chemoattractant protein-1, tumor necrosis factor-α, transforming growth factor beta 1, and vascular endothelial growth factor-A were decreased in the PPARγ group compared to the vehicle group in the early periods of corneal inflammation.
  
  
  CONCLUSIONS
  The ophthalmic solution of the PPARγ agonist inhibited inflammation, decreased the fibrotic reaction, and prevented neovascularization in the cornea from the early phase after alkali burn injury. The ophthalmic solution of the PPARγ agonist may provide a new treatment strategy with useful clinical applications for corneal inflammation and wound healing.
authors.affiliation: Department of Ophthalmology, Nippon Medical School, Tokyo, Japan ; Department of Analytic Human Pathology, Nippon Medical School, Tokyo, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Uchiyama
authors.forename: Akira
authors.initials: A
authors.lastname: Shimizu
authors.forename: Yukinari
authors.initials: Y
authors.lastname: Masuda
authors.forename: Shinya
authors.initials: S
authors.lastname: Nagasaka
authors.forename: Yuh
authors.initials: Y
authors.lastname: Fukuda
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takahashi
mesh_terms: D000468:Alkalies; D000818:Animals; D002057:Burns, Chemical / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D003315:Cornea / Q000187:drug effects / Q000473:pathology*; D016510:Corneal Neovascularization / Q000188:drug therapy / Q000473:pathology; D003318:Corneal Opacity / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D004195:Disease Models, Animal; D005126:Eye Burns / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D005355:Fibrosis; D007249:Inflammation / Q000150:complications / Q000188:drug therapy / Q000517:prevention & control*; D008264:Macrophages / Q000187:drug effects / Q000473:pathology; D008297:Male; D020556:Neutrophil Infiltration / Q000187:drug effects; D009883:Ophthalmic Solutions / Q000494:pharmacology* / Q000627:therapeutic use*; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism; D000077205:Pioglitazone; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D045162:Thiazolidinediones / Q000494:pharmacology / Q000627:therapeutic use; D014945:Wound Healing / Q000187:drug effects
chemical_list: D000468:Alkalies; D018925:Chemokines; D024061:Collagen Type III; D009883:Ophthalmic Solutions; D047495:PPAR gamma; D012333:RNA, Messenger; D045162:Thiazolidinediones; D000077205:Pioglitazone