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M. De Saint Jean, C. Baudouin, F. Brignole, R. De Nicolas, Y. de Kozak; Development and characterization of a new dry eye model in Lewis rat. . Invest. Ophthalmol. Vis. Sci. 2004;45(13):64.
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Purpose: To develop a new dry eye model in Lewis rat combining systemic stimulation of the immune system and topical alteration of ocular surface homeostasis. Methods:Male Lewis rats (8–11 weeks of age) were injected into the footpads with complete Freund’s adjuvant (CFA) supplemented with 250 µg of Mycobacterium tuberculosis H37Ra. Ten days later, daily (3 times a day) instillations of 1.0% atropine sulfate (group 1) or saline (group 2) were performed. In addition, 2 groups of rats received either atropine (group 3) or saline (group 4) without systemic immunization with CFA. Clinical examination of the eyes was performed by slit–lamp examination of the cornea after fluorescein staining and Schirmer I test. The animals were sacrificed 10 days after the beginning of the treatment with atropine or saline and eyes, conjunctivas and lacrymal glands were taken for examination. Cellular infiltration in the conjunctiva was analyzed using conjunctival impression specimens by confocal microscopy examination. In addition, inflammatory modifications of ocular surface tissues were studied by histopathology, immunohistochemistry and flow cytometric analysis of conjunctival cell populations. Results: The association of CFA immunization with instillations of atropine sulfate (group 1) induced a typical tear deficiency resulting in decrease in Schimer I scores and a spot keratitis. As compared to the group 1, atropine–treated animals without CFA (group 3) presented only very slight, fine corneal defects, whereas no keratitis was present in saline–treated animals (group 4). Topical treatment with atropine or saline without CFA immunization (groups 3 and 4 respectively) induced only a slight decrease of Schirmer scores. Impression cytology specimen examination showed a significant increase in the number of squamous, apoptotic cells in the conjunctiva of atropine/CFA–treated animals as compared to saline/CFA–treated animals. Conclusions: The combination of immune stimulation and topical aggression of the ocular surface in vivo produces a complete dry eye syndrome resulting from the global dysfunction of ocular surface–lacrimal system. This model could be very useful in further investigations of mechanism–based treatment of dry eye disease.
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