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Abstract #78948 Published in IGR 20-1

Infection of endotheliotropic human cytomegalovirus of trabecular meshwork cells

Shimizu D; Miyazaki D; Miyazaki D; Shimizu Y; Hosogai M; Kosugi I; Inoue Y
Japanese Journal of Ophthalmology 2018; 62: 667-676


PURPOSE: Human cytomegalovirus (HCMV) infections can cause endotheliitis which is associated with an elevation in the intraocular pressure (IOP). However, the mechanism of the IOP elevation has not been established. The purpose of this study was to determine whether HCMV strains which are capable of infecting corneal endothelial cells can also replicate and induce anti-viral responses, and can reorganize the actin cytoskeleton in trabecular meshwork cells. STUDY DESIGN: Experimental study design. METHODS: Cultured primary human trabecular meshwork cells (HTMCs) were infected with the Towne or TB40/E strains of HCMV. TB40/E is trophic for vascular endothelial and corneal endothelial cells. Real-time PCR, western blot, and fluorescent immunostaining have been used to determine whether HCMV-infected HTMCs will support the expression of viral mRNA and protein, allow viral replication, and elicit anti-viral host responses. We also determined whether lytic replication was present after HCMV infection. RESULTS: HCMV infection led to the expression of viral mRNA and proteins of IE1, glycoprotein B(gB), and pp65. TB40/E infection induced interferon-β, a sign of host anti-viral immune response and monocyte chemotactic protein-1 (MCP-1) as IOP-related chemokine. Together with the induction of the regulators of actin cytoskeleton, myosin phosphatase Rho interacting protein (MPRIP) and MCP-1, TB40/E induced a high level of expression of viral proteins, including IE1, gB, and pp65 as well as actin stress fiber formation, and achieved pathogenically high viral titers. CONCLUSIONS: Human trabecular meshwork cells support the replication of endotheliotropic TB40/E strain of HCMV which indicates that this strain may have high virulence for trabecular meshwork.

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Classification:

2.5.2 Schlemms canal (Part of: 2 Anatomical structures in glaucoma > 2.5 Meshwork)
9.4.6 Glaucomas associated with inflammation, uveitis (Part of: 9 Clinical forms of glaucomas > 9.4 Glaucomas associated with other ocular and systemic disorders)



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