1. Retinal pigment epithelium transcriptome analysis in chronic smoking reveals a suppressed innate immune response and activation of differentiation pathways
- Author
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Sujung Kim, Jiang Qian, Matthew Brooks, Koray Dogan Kaya, Ying Xin, Lei Wang, Jie Wang, Anand Swaroop, and James T. Handa
- 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 - 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.
- Published
- 2020