PURPOSE: To evaluate the therapeutic efficacy of topical interleukin-1 receptor antagonist (IL-1Ra) in the treatment of dry eye disease. DESIGN: Laboratory investigation. METHODS: Dry eye disease was induced in C57BL/6 female mice through exposure to a desiccating environment within a controlled environment chamber. Topical formulations containing 5% IL-1Ra, 1% methylprednisolone, 0.05% cyclosporin A, and a vehicle control containing carboxymethylcellulose sodium were applied after the induction of dry eye. Corneal fluorescein staining was performed by a masked observer in the different treatment groups. Immunohistochemical studies were undertaken to enumerate corneal CD11b+ cells, as well as to evaluate corneal lymphangiogenesis. Real-time polymerase reaction was used to quantify the expression of interleukin-1β in the cornea. RESULTS: A significant decrease in corneal fluorescein staining was observed after topical treatment with 5% IL-1Ra (P < .01), 1% methylprednisolone (P < .01), and 0.05% cyclosporin A (P < .03). Additionally, a significant decrease in the numbers of central corneal CD11b+ cells (P < .05), corneal lymphatic growth (P < .05), and corneal interleukin-1β expression (P < .003), compared with vehicle treated, were demonstrated only after treatment with 5% IL-1Ra and 1% methylprednisolone, and were absent after cyclosporin A treatment. CONCLUSIONS: Topical treatment with IL-1Ra is effective in ameliorating the clinical signs of the dry eye disease, as well as in reducing underlying inflammation. These effects are comparable with those resulting from treatment with topical methylprednisolone. Topical IL-1Ra may hold promise as a novel therapeutic strategy in the treatment of dry eye.
PURPOSE: To evaluate the therapeutic efficacy of topical interleukin-1 receptor antagonist (IL-1Ra) in the treatment of dry eye disease. DESIGN: Laboratory investigation. METHODS:Dry eye disease was induced in C57BL/6 female mice through exposure to a desiccating environment within a controlled environment chamber. Topical formulations containing 5% IL-1Ra, 1% methylprednisolone, 0.05% cyclosporin A, and a vehicle control containing carboxymethylcellulose sodium were applied after the induction of dry eye. Corneal fluorescein staining was performed by a masked observer in the different treatment groups. Immunohistochemical studies were undertaken to enumerate corneal CD11b+ cells, as well as to evaluate corneal lymphangiogenesis. Real-time polymerase reaction was used to quantify the expression of interleukin-1β in the cornea. RESULTS: A significant decrease in corneal fluorescein staining was observed after topical treatment with 5% IL-1Ra (P < .01), 1% methylprednisolone (P < .01), and 0.05% cyclosporin A (P < .03). Additionally, a significant decrease in the numbers of central corneal CD11b+ cells (P < .05), corneal lymphatic growth (P < .05), and corneal interleukin-1β expression (P < .003), compared with vehicle treated, were demonstrated only after treatment with 5% IL-1Ra and 1% methylprednisolone, and were absent after cyclosporin A treatment. CONCLUSIONS: Topical treatment with IL-1Ra is effective in ameliorating the clinical signs of the dry eye disease, as well as in reducing underlying inflammation. These effects are comparable with those resulting from treatment with topical methylprednisolone. Topical IL-1Ra may hold promise as a novel therapeutic strategy in the treatment of dry eye.
Authors: Jerry Y Niederkorn; Michael E Stern; Stephen C Pflugfelder; Cintia S De Paiva; Rosa M Corrales; Jianping Gao; Karyn Siemasko Journal: J Immunol Date: 2006-04-01 Impact factor: 5.422
Authors: C S De Paiva; S Chotikavanich; S B Pangelinan; J D Pitcher; B Fang; X Zheng; P Ma; W J Farley; K F Siemasko; J Y Niederkorn; M E Stern; D-Q Li; S C Pflugfelder Journal: Mucosal Immunol Date: 2009-02-25 Impact factor: 7.313
Authors: Jinzhao Hou; Sharon A Townson; Joseph T Kovalchin; Allyson Masci; Olga Kiner; Yanqun Shu; Bracken M King; Emily Schirmer; Kathryn Golden; Christoph Thomas; K Christopher Garcia; Gregory Zarbis-Papastoitsis; Eric S Furfine; Thomas M Barnes Journal: Proc Natl Acad Sci U S A Date: 2013-02-19 Impact factor: 11.205
Authors: Francisco Amparo; Mohammad H Dastjerdi; Andre Okanobo; Giulio Ferrari; Leila Smaga; Pedram Hamrah; Ula Jurkunas; Debra A Schaumberg; Reza Dana Journal: JAMA Ophthalmol Date: 2013-06 Impact factor: 7.389