Triamcinolone regulated apopto‐phagocytic gene expression patterns in the clearance of dying cells in the retina

Purpose The clearance of dying cells in the retina has known relevance to development of age‐related macular degeneration (AMD). We aimed to investigate the gene expression patterns present during such a clearance process and the effect of triamcinolone (TC) treatment on them. Methods Primary human...

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Bibliographic Details
Published in:Acta ophthalmologica (Oxford, England) England), 2012-09, Vol.90 (s249), p.0-0
Main Authors: PETROVSKI, G, ALBERT, R, KRISTOF, E, ZAHUCZKY, G, BERTA, A, FESUS, L
Format: Article
Language:English
Subjects:
Age
Gene expression
Kinases
Macular degeneration
Ophthalmology
Proteins
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Summary:Purpose The clearance of dying cells in the retina has known relevance to development of age‐related macular degeneration (AMD). We aimed to investigate the gene expression patterns present during such a clearance process and the effect of triamcinolone (TC) treatment on them. Methods Primary human retinal pigment epithelium (hRPE) and ARPE‐19 cells were induced to undergo cell death by loss of extracellular matrix attachment (anoikis). Phagocytic clearance assays of the engulfment of anoikic cells by human monocyte‐derived macrophages (HMDMs) were performed in the presence or absence of TC. Phagocytosis was quantified using a standard double‐staining method on flow cytometry. TaqMan low‐density array determining the gene expression of known markers of phagocytosis was carried out in HMDMs engulfing anoikic cells. Loss‐of‐function studies using siRNA were also performed on selected apopto‐phagocytic genes. Results The glucocorticoid TC had a profound phagocytosis‐enhancing effect on HMDMs engulfing anoikic hRPE or ARPE‐19 cells, causing a selective upregulation of the Mer tyrosine kinase (MERTK) receptor, while decreasing the expression of the AXL receptor tyrosine kinase and THSB‐1 (phagocytosis bridging molecule). Similar expression patterns were also observed in the anoikic cells. The key role of the MERTK could be demonstrated in HMDMs engulfing the dying cells using gene silencing as well as blocking antibodies. Conclusion Specific agonists of the tyrosine kinase receptors may have a potential role as phagocytosis enhancers in the retina and serve as future targets for AMD therapy.
ISSN:1755-375X
1755-3768
DOI:10.1111/j.1755-3768.2012.4483.x