Abstract
Purpose:
To determine whether human cytomegalovirus (CMV) can infect corneal endothelial cells, and characterize inflammatory responses of corneal endothelial cells after infection.
Methods:
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.
Results:
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.
Conclusions:
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.
Keywords: 492 cytomegalovirus •
481 cornea: endothelium