title: Efficacy of a new topical cationic emulsion of cyclosporine A on dry eye clinical signs in an experimental mouse model of dry eye.
abstract: Dry eye disease (DED) is a complex, multifactorial pathology characterized by corneal epithelium lesions and inflammation. The aim of the present study was to evaluate the efficacy of a cationic emulsion of cyclosporine A (CsA) in a mouse model that mimics severe dry eye. Eight to 12-week-old female C57BL/6N mice with tail patches of scopolamine were housed in controlled environment chambers to induce dry eye. At day three, following dry eye confirmation by corneal fluorescein staining (CFS, score 0-15) and phenol red thread (PRT) lacrimation test, the mice (n = 10/gp) were either treated 3 times a day in both eyes with drug-free cationic emulsion, a 0.1% CsA cationic emulsion, or 1% methylprednisolone (positive control), or non-treated. Aqueous tear production and CFS scores were evaluated at baseline and throughout the treatment period. The lacrimation test confirmed the scopolamine-induced decrease in aqueous production by the lacrimal gland. A reduction of 59% in induced-CFS was observed following topical treatment with 0.1% CsA. The beneficial effect of the cationic emulsion vehicle itself on keratitis was also clearly evidenced by its better performance over 1% methylprednisolone, -36%, vs. -28% on the CFS scores, respectively. This study indicates that the cationic emulsion of CsA (0.1%) was a very effective formulation for the management of corneal epithelium lesions in a severe DED mouse model. In addition, it performed better than a potent glucocorticosteroid (1% methylprednisolone). This cationic emulsion of CsA (0.1%), combining CsA and a tear film oriented therapy (TFOT), i.e. with vehicle properties that mechanically stabilize the tear film, represents a promising new treatment strategy for the management of the signs of dry eye.
authors: SANTEN SAS, Novagali Innovation Center, 1, rue Pierre Fontaine, Bâtiment Genavenir IV, F-91458 Evry Cedex, France.
authors: Philippe
authors: P
authors: Daull
authors: Iris Pharma, Les Nertières, Allée Hector Pintus, F-06610 La Gaude, France.
authors: Laurence
authors: L
authors: Feraille
authors: Clinica Oculistica, Di.N.O.G.M.I., Azienda Ospedaliera Universitaria San Martino-IST, Genoa, Italy.
authors: Stefano
authors: S
authors: Barabino
authors: Iris Pharma, Les Nertières, Allée Hector Pintus, F-06610 La Gaude, France.
authors: Nicolas
authors: N
authors: Cimbolini
authors: Iris Pharma, Les Nertières, Allée Hector Pintus, F-06610 La Gaude, France.
authors: Sophie
authors: S
authors: Antonelli
authors: Iris Pharma, Les Nertières, Allée Hector Pintus, F-06610 La Gaude, France.
authors: Virgine
authors: V
authors: Mauro
authors: SANTEN SAS, Novagali Innovation Center, 1, rue Pierre Fontaine, Bâtiment Genavenir IV, F-91458 Evry Cedex, France. Electronic address: jean-sebastien.garrigue@santen.fr.
authors: Jean-Sébastien
authors: JS
authors: Garrigue
mesh_terms: D000287:Administration, Topical; D000818:Animals; D003315:Cornea / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016572:Cyclosporine / Q000008:administration & dosage*; D004195:Disease Models, Animal; D015352:Dry Eye Syndromes / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism; D004655:Emulsions; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D051379:Mice; D008810:Mice, Inbred C57BL; D013666:Tears / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D004655:Emulsions; D007166:Immunosuppressive Agents; D016572:Cyclosporine
keywords: Cationic emulsion; Cornea; Cyclosporine A; Dry eye; Mouse model