Universität zu Köln

Gehlsen, Uta ORCID: 0000-0001-9057-9199, Braun, Tobias, Notara, Maria, Kroesser, Sonja and Steven, Philipp (2017). A semifluorinated alkane (F4H5) as novel carrier for cyclosporine A: a promising therapeutic and prophylactic option for topical treatment of dry eye. Graefes Arch. Clin. Exp. Ophthalmol., 255 (4). S. 767 - 776. NEW YORK: SPRINGER. ISSN 1435-702X

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Abstract

Cyclosporine A (Cs) has been used as effective topical therapy for inflammatory dry eye disease since more than a decade. However, due to its lipophilic character, Cs is formulated as emulsions or oily solutions for topical application. This experimental study aimed to test if the use of semifluorinated alkanes (SFAs) as a preservative-free, well-tolerated non-stinging or burning vehicle maintains or even improves the benefits of Cs in the topical therapy of dry-eye disease. Desiccating stress was applied to C57BL/6 mice for 14 consecutive days to induce experimental dry-eye. Cs dissolved in SFA (perfluorobutylpentane = F4H5with 0.5% Ethanol), F4H5 with 0.5% ethanol only, 0.05% Cs (RestasisA (R)), and dexamethasone (MonodexA (R)) were applied three times daily beginning either at day 4 or day 11 of desiccating stress for up to 3 weeks after end of dry-eye induction. In comparison to other groups, Cs/F4H5 demonstrated high efficacy and earlier reduction of corneal staining. In this study, Cs/F4H5 had the ability to maintain conjunctival goblet cell density once applied on day 4. Flow cytometry analysis from cervical lymphnodes demonstrated a significantly lower CD4+ and CD8+ T-cells in the Cs/F4H5 group following 3 weeks of therapy than at baseline, but no difference in regulatory T cells from regional lymphnodes were seen. Overall, compared to a commercially available Cs formulation (RestasisA (R)) and dexamethasone, Cs/F4H5 was shown to be equally effective but with a significantly faster therapeutic response in reducing signs of dry-eye disease in an experimental mouse model.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Gehlsen, Uta UNSPECIFIED orcid.org/0000-0001-9057-9199 UNSPECIFIED Braun, Tobias UNSPECIFIED UNSPECIFIED UNSPECIFIED Notara, Maria UNSPECIFIED UNSPECIFIED UNSPECIFIED Kroesser, Sonja UNSPECIFIED UNSPECIFIED UNSPECIFIED Steven, Philipp UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-235329
DOI:	10.1007/s00417-016-3572-y
Journal or Publication Title:	Graefes Arch. Clin. Exp. Ophthalmol.
Volume:	255
Number:	4
Page Range:	S. 767 - 776
Date:	2017
Publisher:	SPRINGER
Place of Publication:	NEW YORK
ISSN:	1435-702X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language OCULAR SURFACE; DESICCATING STRESS; MOUSE MODEL; T-CELLS; LACRIMAL KERATOCONJUNCTIVITIS; SJOGRENS-SYNDROME; TEAR PRODUCTION; DISEASE; INFLAMMATION; EFFICACY Multiple languages Ophthalmology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/23532