Optimization and validation of an existing, surgical and robust dry eye rat model for the evaluation of therapeutic compounds

Autor: Peter Delputte, Jurgen Joossens, Nadia Zakaria, Ingrid De Meester, Ellen Lanckacker, Anne-Marie Lambeir, Carina Koppen, Nathalie Cools, Paul Cos, Cedric Joossen, Louis Maes
Rok vydání: 2015
Předmět:
0301 basic medicine
Pathology
medicine.medical_specialty
Conjunctiva
genetic structures
Rat model
Anti-Inflammatory Agents
Cyclosporins
Lacrimal gland
Dexamethasone
03 medical and health sciences
Cellular and Molecular Neuroscience
0302 clinical medicine
Animal model
Surgical removal
medicine
Animals
Rats
Wistar
Fluorescence staining
business.industry
Tumor Necrosis Factor-alpha
Lacrimal Apparatus
medicine.disease
Immunohistochemistry
Sensory Systems
eye diseases
Rats
Ophthalmology
Disease Models
Animal
030104 developmental biology
medicine.anatomical_structure
Matrix Metalloproteinase 9
Tears
030221 ophthalmology & optometry
Cytokines
Dry Eye Syndromes
Female
Fluorescein
sense organs
Human medicine
Gradual increase
Ophthalmic Solutions
business
Infiltration (medical)
Immunosuppressive Agents
Zdroj: Experimental eye research
ISSN: 1096-0007
0014-4835
Popis: 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.
Databáze: OpenAIRE
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