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Michiko Kandori, Dai Miyazaki, Keiko Yakura, Yumiko Noguchi, Yukimi Yamamoto, Yoshitsugu Inoue, Tatsuo Suzutani; Human Cytomegalovirus-mediated inflammatory responses of corneal endothelial cells. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1651.
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© ARVO (1962-2015); The Authors (2016-present)
To determine whether human cytomegalovirus (CMV) can infect corneal endothelial cells, and characterize inflammatory responses of corneal endothelial cells after infection.
Clinical isolate of CMV was purified by density gradient and adsorbed to immortalized human corneal endothelial cells (HCEn) at a multiplicity of infection 0, 0.01 or 0.1. The infectivity of CMV into HCEn cells was analyzed by the induction of immediate-early, early, and late genes of CMV, and inflammatory cytokine induction by real-time RT-PCR. Inflammatory responses of HCEn cells were characterized by protein array analysis of the supernatants.
Representative viral genes, including IE-1, UL-83, and glycoprotein B, were sequentially induced after CMV infection. CMV infection characteristically stimulated induction of IL-6 and IDO1 (indoleamine 2,3-dioxygenase 1) mRNA by HCEn cells. Protein array analysis showed significant induction of inflammatory mediators, immune regulators, or neurotrophic factors , including BDNF, BLC, GDNF, PIGF, MCP-1, EGF, TGF-β1, PDGF-BB, IL-16, Leptin, MCSF, MCP-4, IP-10, IL-6, IL-13, IL-5, IL-15, GCP-2, FGF-9, IFN-γ, RANTES, Ckβ8-1, Eotaxin, MIP-3α, VEGF.
CMV infects corneal endothelial cells, and provokes anti-viral responses, together with induction of immune regulatory mediators or neurotrophic factors. These results may give us clues to elucidate the pathogenesis of CMV endotheliitis.
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