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Philippe Daull, Laurence Feraille, Karima Kessal, Pierre-Paul Elena, Stefano Barabino, Christophe Baudouin, Jean-Sebastien Garrigue; Corneal transcriptome changes in a mouse model of dry eye. Invest. Ophthalmol. Vis. Sci. 2017;58(8):797.
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© ARVO (1962-2015); The Authors (2016-present)
Dry eye disease (DED) is a complex multifactorial disease that affects the life of millions of people worldwide. The loss of the ocular surface homeostasis results in the activation of inflammatory pathways leading to corneal epithelium alterations. The aim of the present study was to explore how dry eye modulates the corneal expression profiles of inflammation-associated genes in a mouse model of dry eye with severe corneal epithelium lesions.
Eight to 12-week-old female C57BL6 mice with tail patches of scopolamine (replaced every other days) were housed in controlled environment room 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) were left untreated for an additional 7 days in the dry eye environment. At the end of the experiment the cornea were collected on ice, snap frozen in liquid nitrogen and stored at -80°C before processing. The cornea of 10 aged-matched healthy female C57BL6 mice served as controls. Following mRNA extraction (Qiagen RNeasy mini kit) and RNA integrity assessment (Agilent Bioanalyzer), the expressed transcripts were analyzed using a nCounter mouse inflammation code set (NanoString).
The PRT lacrimation test confirmed the scopolamine-induced decrease in tear secretion for the dry eye environment mice. At the end of the treatment period, the CFS score of the dry eye mice was 11.2±1.5 (CFS score range; 9-14), confirming the severity of the disease. 34 genes were upregulated (1.5- to 28.7-fold), and 34 were down regulated (0.7- to <0.1-fold). Of particular interest were the genes: Cxcl1, Ccl2, Fos, Areg, Il1b, Ptgs2, Jun, Tnfaip3, Tnf, Myc, Cebpb, Relb, Maff, Il1a, Irf1, Map2k6, Nod1, Csf1, Ccr2, which were significantly modulated (up or down) by the dry eye condition.
This study shed new lights on the pathways associated with the development of corneal damages in a mouse model of dry eye and identified possible new targets for the management of dry eye disease in patients.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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