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Ex Vivo Organotypic Corneal Model of Acute Epithelial Herpes Simplex Virus Type I Infection
Published on: November 3, 2012
[Apoptosis in human non-necrotizing stromal herpes simplex keratitis]
A Heiligenhaus1, S Mrzyk, D Bauer
1Augenabteilung, St. Franziskus-Hospital, Münster. arnd.heiligenhaus@uni-essen.de
Summary
Herpes simplex virus (HSV-1) keratitis involves apoptotic cell death in the cornea. The Fas-FasL system likely contributes to this process, potentially limiting viral spread.
Area of Science:
- Ophthalmology
- Immunology
- Virology
Background:
- Herpes simplex virus (HSV-1) stromal keratitis is an immune-mediated corneal disease.
- HSV-1 infection is known to induce apoptosis in cells.
- This study investigated apoptotic cell death in HSV-1 stromal keratitis patient samples.
Purpose of the Study:
- To investigate the presence and role of apoptotic cell death in HSV-1 stromal keratitis.
- To examine the involvement of the Fas-FasL system in the pathogenesis of HSV-1 keratitis.
Main Methods:
- Analysis of keratectomy specimens from patients with HSV-1 stromal keratitis and healthy controls.
- Histological analysis and immunoperoxidase staining for HSV-1, Fas, and FasLigand (FasL) antigens.
- Assessment of apoptosis using the TUNEL assay.
Main Results:
- Apoptotic cells were found in the inflammatory infiltrates and epithelium of HSV-1 diseased corneas, unlike healthy corneas.
- Fas was detected in all corneal cell layers and inflammatory cells, while FasL was localized to areas of inflammation.
- HSV-1 antigen was detected in only one specimen, suggesting the immune response plays a significant role.
Conclusions:
- Apoptosis is implicated in the pathogenesis of HSV-1 stromal keratitis.
- The Fas-FasL system appears to be involved in inducing apoptosis during HSV-1 keratitis.
- Apoptosis may help deplete inflammatory cells and limit viral replication within the cornea.
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Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or immature dendritic cells. Non-professional phagocytes such as epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes.
Normal cells contain receptors that prevent them from being recognized by phagocytes.
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Necrosis is considered as an “accidental” or unexpected form of cell death that ends in cell lysis. The first noticeable mention of “necrosis” was in 1859 when Rudolf Virchow used this term to describe advanced tissue breakdown in his compilation titled “Cell Pathology”.
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