TY - JOUR
T1 - Safety and efficacy of topical infliximab in a mouse model of ocular surface scarring
AU - Ferrari, Giulio
AU - Bignami, Fabio
AU - Giacomini, Chiara
AU - Franchini, Stefano
AU - Rama, Paolo
PY - 2013
Y1 - 2013
N2 - 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-1b 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.
AB - 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-1b 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.
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U2 - 10.1167/iovs.12-10782
DO - 10.1167/iovs.12-10782
M3 - Article
C2 - 23404121
AN - SCOPUS:84874611029
VL - 54
SP - 1680
EP - 1688
JO - Investigative Ophthalmology and Visual Science
JF - Investigative Ophthalmology and Visual Science
SN - 0146-0404
IS - 3
ER -