1. Effects of ROCK Inhibitors on Apoptosis of Corneal Endothelial Cells in CMV-Positive Posner-Schlossman Syndrome Patients.
- Author
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Igarashi N, Honjo M, Kaburaki T, and Aihara M
- Subjects
- Adult, Aged, Aged, 80 and over, Amides pharmacology, Aqueous Humor metabolism, Aqueous Humor virology, Blotting, Western, Cells, Cultured, Cytokines metabolism, Cytomegalovirus isolation & purification, Cytomegalovirus Infections metabolism, Cytomegalovirus Infections virology, Endothelium, Corneal metabolism, Endothelium, Corneal virology, Eye Infections, Viral metabolism, Eye Infections, Viral virology, Female, Humans, Immunohistochemistry, Iridocyclitis metabolism, Iridocyclitis virology, Isoquinolines pharmacology, Male, Middle Aged, Multiplex Polymerase Chain Reaction, Prospective Studies, Pyridines pharmacology, Sulfonamides pharmacology, rhoA GTP-Binding Protein metabolism, Apoptosis drug effects, Cytomegalovirus Infections pathology, Endothelium, Corneal pathology, Enzyme Inhibitors pharmacology, Eye Infections, Viral pathology, Iridocyclitis pathology, rho-Associated Kinases antagonists & inhibitors
- Abstract
Purpose: To examine the role of aqueous tumor necrosis factor α (TNF-α)-RhoA-Rho kinase (ROCK) signaling in cytomegalovirus (CMV)-induced apoptosis and the barrier function of cultured human corneal endothelial cells (hCECs) in CMV-positive Posner-Schlossman syndrome (CMV+/PSS) patients., Methods: Aqueous levels of TNF-α, IL-8, IL-10, and several other cytokines in 19 CMV+/PSS patients and 20 healthy control subjects were quantitated using a multiplex assay. The expression of active RhoA in hCECs post-CMV infection was determined using western blotting (WB). The expression levels of TNF-α and nuclear factor kappa B (NF-κB) in CMV-infected hCECs were examined by immunocytochemistry (ICC) and WB with and without ROCK inhibitors. The apoptotic rate and barrier integrity in CMV-infected hCECs were also examined., Results: The expression levels of TNF-α, monocyte chemoattractant protein-1 (MCP-1), IL-8, and IL-10 were upregulated in the aqueous humor of CMV+/PSS patients, and among these upregulated cytokines aqueous TNF-α was negatively correlated with the number of corneal endothelial cells. In CMV-infected hCECs, upregulation of TNF-α and NF-κB was determined by WB and ICC. In hCECs, CMV infection induced apoptosis and significantly impaired cell-cell contacts, effects that were attenuated by treatment with a ROCK inhibitor., Conclusions: Aqueous TNF-α was upregulated in CMV+/PSS patients, which may have triggered corneal endothelial cell loss. Modulation of TNF-α, including its downstream Rho-ROCK signaling, could serve as a novel treatment modality for corneal endothelial cell loss in CMV+/PSS patients.
- Published
- 2020
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