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X. Yuan, B. Mitchell, K. Wilhelmus; Molecular Signaling Pathways During Experimental Candida Albicans Keratitis. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2475. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate the genetic expression profile during the early stage of posttraumatic Candida albicans keratitis in inbred mice.
Following unilateral superficial corneal scarification of BALB/c mice, eyes were topically exposed to wild-type C. albicans (SC5314) or were mock-inoculated. After 24 hours, corneas were excised and pooled in sets of five for RNA extraction. Each experimental group was examined in triplicate by microarray using Affymetrix GeneChips® Mouse Expression Set 430, which screens for 45,101 potential murine gene transcripts. A twofold or greater difference (P < 0.05) between fungal-infected corneas compared to mock-infected controls was set as the cutoff criteria for significance. Real-time PCR was used to confirm selective gene expression patterns.
Among all tested murine genes 1,514 (3.4%) transcripts changed significantly during early infection. Inhibitory regulators of the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway were significantly altered (P < .0001), including suppressors of cytokine signaling (SOCS3 and SOCS7). Genes involved in interleukin-2, interleukin-4, granulocyte-macrophage-colony stimulating factor, epidermal growth factor, and vascular endothelial growth factor pathways were significantly upregulated (P < .005). Fungal infected corneas also had increased gene expression by tenfold for tumor necrosis factor-alpha and by twofold for matrix metalloproteinase 9.
Cytokine signaling within the cornea, including genetic downregulation of the JAK/STAT pathway and increased expression of genes regulating interleukins and growth factors, occurred during the initial pathogenesis of experimental C. albicans keratitis.
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