title: Optimization and validation of an existing, surgical and robust dry eye rat model for the evaluation of therapeutic compounds.
abstract: The aim of this research was to optimize and validate an animal model for dry eye, adopting clinically relevant evaluation parameters. Dry eye was induced in female Wistar rats by surgical removal of the exorbital lacrimal gland. The clinical manifestations of dry eye were evaluated by tear volume measurements, corneal fluorescein staining, cytokine measurements in tear fluid, MMP-9 mRNA expression and CD3(+) cell infiltration in the conjunctiva. The animal model was validated by treatment with Restasis(®) (4 weeks) and commercial dexamethasone eye drops (2 weeks). Removal of the exorbital lacrimal gland resulted in 50% decrease in tear volume and a gradual increase in corneal fluorescein staining. Elevated levels of TNF-α and IL-1α have been registered in tear fluid together with an increase in CD3(+) cells in the palpebral conjunctiva when compared to control animals. Additionally, an increase in MMP-9 mRNA expression was recorded in conjunctival tissue. Reference treatment with Restasis(®) and dexamethasone eye drops had a positive effect on all evaluation parameters, except on tear volume. This rat dry eye model was validated extensively and judged appropriate for the evaluation of novel compounds and therapeutic preparations for dry eye disease.
authors.affiliation: Faculty of Pharmaceutical, Biomedical and Veterinary Sciences: Laboratory of Microbiology, Parasitology and Hygiene (LMPH); University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium.
authors.forename: Cedric
authors.initials: C
authors.lastname: Joossen
authors.affiliation: Faculty of Pharmaceutical, Biomedical and Veterinary Sciences: Laboratory of Microbiology, Parasitology and Hygiene (LMPH); University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium.
authors.forename: Ellen
authors.initials: E
authors.lastname: Lanckacker
authors.affiliation: Department of Ophthalmology, Antwerp University Hospital, Wilrijkstraat 10, 2650 Edegem, Belgium; Faculty of Health Sciences and Medicine: Laboratory of Ophthalmology, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium.
authors.forename: Nadia
authors.initials: N
authors.lastname: Zakaria
authors.affiliation: Department of Ophthalmology, Antwerp University Hospital, Wilrijkstraat 10, 2650 Edegem, Belgium.
authors.forename: Carina
authors.initials: C
authors.lastname: Koppen
authors.affiliation: Faculty of Pharmaceutical, Biomedical and Veterinary Sciences: Laboratory of Medicinal Chemistry, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium.
authors.forename: Jurgen
authors.initials: J
authors.lastname: Joossens
authors.affiliation: Laboratory of Experimental Hematology, Vaccine & Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine and Health Sciences, University of Antwerp, 2610 Wilrijk, Belgium.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Cools
authors.affiliation: Faculty of Pharmaceutical, Biomedical and Veterinary Sciences: Laboratory of Medical Biochemistry, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium.
authors.forename: Ingrid
authors.initials: I
authors.lastname: De Meester
authors.affiliation: Faculty of Pharmaceutical, Biomedical and Veterinary Sciences: Laboratory of Medical Biochemistry, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Lambeir
authors.affiliation: Faculty of Pharmaceutical, Biomedical and Veterinary Sciences: Laboratory of Microbiology, Parasitology and Hygiene (LMPH); University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium.
authors.forename: Peter
authors.initials: P
authors.lastname: Delputte
authors.affiliation: Faculty of Pharmaceutical, Biomedical and Veterinary Sciences: Laboratory of Microbiology, Parasitology and Hygiene (LMPH); University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium.
authors.forename: Louis
authors.initials: L
authors.lastname: Maes
authors.affiliation: Faculty of Pharmaceutical, Biomedical and Veterinary Sciences: Laboratory of Microbiology, Parasitology and Hygiene (LMPH); University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium. Electronic address: Paul.cos@uantwerpen.be.
authors.forename: Paul
authors.initials: P
authors.lastname: Cos
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D003228:Conjunctiva / Q000378:metabolism; D003524:Cyclosporins / Q000627:therapeutic use*; D016207:Cytokines / Q000378:metabolism; D003907:Dexamethasone / Q000627:therapeutic use*; D004195:Disease Models, Animal; D015352:Dry Eye Syndromes / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D019793:Fluorescein / Q000378:metabolism; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007765:Lacrimal Apparatus / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009883:Ophthalmic Solutions / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013666:Tears / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D003524:Cyclosporins; D016207:Cytokines; D007166:Immunosuppressive Agents; D009883:Ophthalmic Solutions; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D020780:Matrix Metalloproteinase 9; D019793:Fluorescein
keywords: Animal model; DED; Dry eye disease; KCS; Rat