PURPOSE: 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.
PURPOSE: 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: Paige J LeValley; Bryan P Sutherland; Jennifer Jaje; Sandra Gibbs; Mark Jones; Rikhav Gala; Christopher J Kloxin; Kristi L Kiick; April M Kloxin Journal: ACS Appl Bio Mater Date: 2020-09-17
Authors: Danial Roshandel; Medi Eslani; Alireza Baradaran-Rafii; Albert Y Cheung; Khaliq Kurji; Sayena Jabbehdari; Alejandra Maiz; Setareh Jalali; Ali R Djalilian; Edward J Holland Journal: Ocul Surf Date: 2018-06-20 Impact factor: 5.033
Authors: Claes H Dohlman; Fabiano Cade; Caio V Regatieri; Chengxin Zhou; Fengyang Lei; Alja Crnej; Mona Harissi-Dagher; Marie-Claude Robert; George N Papaliodis; Dongfeng Chen; James V Aquavella; Esen K Akpek; Anthony J Aldave; Kimberly C Sippel; Donald J DʼAmico; Jan G Dohlman; Per Fagerholm; Liqiang Wang; Lucy Q Shen; Miguel González-Andrades; James Chodosh; Kenneth R Kenyon; C Stephen Foster; Roberto Pineda; Samir Melki; Kathryn A Colby; Joseph B Ciolino; Demetrios G Vavvas; Shigeru Kinoshita; Reza Dana; Eleftherios I Paschalis Journal: Cornea Date: 2018-02 Impact factor: 3.152