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Karima Kessal, Philippe Daull, Laurence Feraille, Nicolas Cimbolini, Hong Liang, Mylene Docquier, Stefano Barabino, Stephane Melik Parsadaniantz, Jean-Sebastien Garrigue, CRISTOPHE BAUDOUIN, Françoise Baudouin; Comparison of inflammatory gene networks in dry eye between human and mouse. Invest. Ophthalmol. Vis. Sci. 2019;60(9):274. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
The use of mice in biomedical research to study human diseases and test drugs needs to take into account the differences between species. Hence, we performed a retrospective analysis of 56 inflammatory genes previously identified in human conjunctival cells versus their mouse homologues expressed in the cornea in 3 dry eye (DE) mouse models.
The 3 DE models (I to III) used C57/BL6 mice; I: scopolamine administration associated with a controlled environment exposure for 10 days (n=10); II and III: twice daily instillations for 5 days of hyperosmolar (550 mOsM) NaCl (n=11), and 0.1% benzalkonium chloride (n=10). Control mice (n=12) did not receive any treatment. Total RNAs were extracted from corneas and mRNA copies counted with the mouse inflammation CodeSet (NanoString nCounter). Retrospective statistical analysis comparing the mouse models with the human data was performed using Mann-Whitney non-parametric tests; a p<0.05 was considered significant.
Among the 56 human genes, 45 of their counterpart were detected in the DE mouse corneas. Nevertheless, Ccl4, Ccl5, Ccl22, Ccl24, Cxcl9, Cxcl10, Il23a, Ccr1, H2-Ea-ps, Nox1 and Hsh2d were not expressed in mouse corneas. Among the 45 inflammatory genes expressed by DE mouse corneas, 24 show a significant differential expression (vs control) in the 3 DE models. The genes in common or specific to each group in the different DE models are: 1) Group I, II, III: Mx1, Irf1, Il1rn, Tnfaip3, Keap1 and Mapk8; 2) Group II, III: Tlr3, Nfatc3, Mapkapk2; 3) Group I, II: Mek6; 4) Group I: Tnfa, Myd88, Prkca, Maff; 5) Group II: Ltb4r2, H2-Eb1, Ptgfr, Ly96, Traf2, Stat3, Hmgb1, Atf2; 6) Group III: Tradd, Ripk2, Plcb1. These results suggest that: 1) 24/45 genes of the human genes are similarly significantly modulated in the mouse; 2) the different DE models have a common network of genes expressed in the corneas; 3) each DE mouse model expresses a set of genes specific to the ocular stress used to generate DE.
This translational research confirms the usefulness of the mouse as an animal model for studying the underlying mechanisms of DE and for assessing the role of each of the gene identified in humans. This kind of comparative gene expression analysis is a useful strategy to evaluate consistency between species, and should be done to evaluate correctly the most appropriate mouse models to better decipher DE and screen potential new therapeutics.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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