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Retinal pigment epithelium transcriptome analysis in chronic smoking reveals a suppressed innate immune response and activation of differentiation pathways
- Source :
- Free Radic Biol Med
- Publication Year :
- 2020
-
Abstract
- Cigarette smoking, a powerful mixture of chemical oxidants, is the strongest environmental risk factor for developing age-related macular degeneration (AMD), the most common cause of blindness among the elderly in western societies. Despite intensive study, the full impact of smoking on the retinal pigment epithelium (RPE), a central cell type involved in AMD pathobiology, remains unknown. The relative contribution of the known dysfunctional pathways to AMD, at what stage they are most pathogenic, or whether other processes are relevant, is poorly understood, and furthermore, whether smoking activates them, is unknown. We performed global RNA-sequencing of the RPE from C57BL/6J mice exposed to chronic cigarette smoke for 6 months to identify potential pathogenic and cytoprotective pathways. The RPE transcriptome induced by chronic cigarette smoking exhibited a mixed response of marked suppression of the innate immune response including type I and II interferons and upregulation of cell differentiation and morphogenic gene clusters, suggesting an attempt by the RPE to maintain its differentiated state despite smoke-induced injury. Given that mice exposed to chronic smoke develop early features of AMD, these novel findings are potentially relevant to the transition from aging to AMD.
- Subjects :
- 0301 basic medicine
Cell type
Cellular differentiation
Retinal Pigment Epithelium
Biology
Biochemistry
Article
Transcriptome
03 medical and health sciences
Mice
0302 clinical medicine
Downregulation and upregulation
Physiology (medical)
medicine
Animals
Gene
Innate immune system
Retinal pigment epithelium
Gene Expression Profiling
Smoking
Cell Differentiation
Macular degeneration
medicine.disease
eye diseases
Immunity, Innate
Mice, Inbred C57BL
030104 developmental biology
medicine.anatomical_structure
Immunology
sense organs
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 18734596
- Volume :
- 156
- Database :
- OpenAIRE
- Journal :
- Free radical biologymedicine
- Accession number :
- edsair.doi.dedup.....4639d5b10096b8c283ba353fda4758ac