title: Safety and efficacy of topical infliximab in a mouse model of ocular surface scarring.
abstract: OBJECTIVE
  To evaluate the safety/efficacy of topical infliximab, an anti-TNF-α monoclonal antibody, in a mouse model of ocular surface scarring.
  
  
  METHODS
  Twenty alkali burn mice were treated with infliximab (10 mg/mL) topically 6 times a day, while 20 alkali burn mice received saline for 7 days. Corneal opacity, epithelial wound healing, and ocular phimosis were examined at the slit-lamp. Tear production was quantified with phenol red thread test. Immunofluorescence for infliximab penetration, TNF-α localization, CD45+ cell infiltration, PAS, and Masson's trichrome staining were evaluated on ocular globes and eyelids. TNF-α and IL-1β expression levels were measured on treated murine corneas and eyelids. Finally, quantification of corneal CD31+ blood vessels and LYVE1+ lymphatic vessels were evaluated on 10 additional alkali burn mice receiving either infliximab or saline, after 14 days.
  
  
  RESULTS
  Topical infliximab penetrated the cornea and the conjunctiva and was not toxic (negative fluorescein stain). Its molecular target, TNF-α, was detected in the cornea after injury. Infliximab significantly reduced corneal perforation, opacity index, phimosis, leukocyte infiltration, and fibrosis in the eyelids. It also significantly prevented goblet cell infiltration in epithelial cornea and loss in the conjunctiva (P < 0.05), improved tear secretion and epithelial healing (P < 0.05). Finally, it significantly reduced both corneal hem- (P < 0.05) and lymphangiogenesis (P < 0.01).
  
  
  CONCLUSIONS
  Infliximab penetrates the cornea and is safe to the ocular surface in an animal model of ocular surface scarring. We suggest that topical application of infliximab may be a useful treatment in ocular caustications.
authors: Cornea and Ocular Surface Disease Unit, Eye Repair Lab, San Raffaele Hospital, Via Olgettina 60, Milan, Italy. ferrari.giulio@hsr.it
authors: Giulio
authors: G
authors: Ferrari
authors: Fabio
authors: F
authors: Bignami
authors: Chiara
authors: C
authors: Giacomini
authors: Stefano
authors: S
authors: Franchini
authors: Paolo
authors: P
authors: Rama
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D002057:Burns, Chemical / Q000188:drug therapy* / Q000473:pathology; D003228:Conjunctiva / Q000473:pathology; D003315:Cornea / Q000378:metabolism / Q000473:pathology; D016510:Corneal Neovascularization / Q000517:prevention & control; D005126:Eye Burns / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D005143:Eyelids / Q000378:metabolism; D005260:Female; D005355:Fibrosis / Q000517:prevention & control; D020397:Goblet Cells / Q000187:drug effects; D000069285:Infliximab; D053583:Interleukin-1beta / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects; D042583:Lymphangiogenesis / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D011897:Random Allocation; D013666:Tears / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000911:Antibodies, Monoclonal; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab