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Effects of ROCK Inhibitors on Apoptosis of Corneal Endothelial Cells in CMV-Positive Posner-Schlossman Syndrome Patients.
- Source :
-
Investigative ophthalmology & visual science [Invest Ophthalmol Vis Sci] 2020 Aug 03; Vol. 61 (10), pp. 5. - Publication Year :
- 2020
-
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.<br />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.<br />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.<br />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.
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 1552-5783
- Volume :
- 61
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Investigative ophthalmology & visual science
- Publication Type :
- Academic Journal
- Accession number :
- 32749463
- Full Text :
- https://doi.org/10.1167/iovs.61.10.5