Retinal pigment epithelium transcriptome analysis in chronic smoking reveals a suppressed innate immune response and activation of differentiation pathways

Lei Wang; Koray D Kaya; Sujung Kim; Matthew J Brooks; Jie Wang; Ying Xin; Jiang Qian; Anand Swaroop; James T Handa

doi:10.1016/j.freeradbiomed.2020.06.004

Retinal pigment epithelium transcriptome analysis in chronic smoking reveals a suppressed innate immune response and activation of differentiation pathways

Free Radic Biol Med. 2020 Aug 20:156:176-189. doi: 10.1016/j.freeradbiomed.2020.06.004. Epub 2020 Jul 4.

Authors

Lei Wang¹, Koray D Kaya², Sujung Kim³, Matthew J Brooks⁴, Jie Wang⁵, Ying Xin⁶, Jiang Qian⁷, Anand Swaroop⁸, James T Handa⁹

Affiliations

¹ Wilmer Eye Institute, Johns Hopkins University, Baltimore, MD, USA. Electronic address: lwang9@jhmi.edu.
² Neurobiology, Neurodegeneration & Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD, 20892, USA. Electronic address: koraydogan.kaya@nih.gov.
³ Wilmer Eye Institute, Johns Hopkins University, Baltimore, MD, USA. Electronic address: sjun6@jhmi.edu.
⁴ Neurobiology, Neurodegeneration & Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD, 20892, USA. Electronic address: brooksma@nei.nih.gov.
⁵ Wilmer Eye Institute, Johns Hopkins University, Baltimore, MD, USA. Electronic address: jwang240@jhmi.edu.
⁶ Wilmer Eye Institute, Johns Hopkins University, Baltimore, MD, USA. Electronic address: yingxinac@gmail.com.
⁷ Wilmer Eye Institute, Johns Hopkins University, Baltimore, MD, USA. Electronic address: jiang.qian@jhmi.edu.
⁸ Neurobiology, Neurodegeneration & Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD, 20892, USA. Electronic address: swaroopa@nei.nih.gov.
⁹ Wilmer Eye Institute, Johns Hopkins University, Baltimore, MD, USA. Electronic address: jthanda@jhmi.edu.

PMID: 32634473
PMCID: PMC7434665
DOI: 10.1016/j.freeradbiomed.2020.06.004

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.

Keywords: Age-related macular degeneration; Aging; Differentiation; Innate immunity; RNA sequencing; Smoking.

Publication types

Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Differentiation
Gene Expression Profiling
Immunity, Innate / genetics
Mice
Mice, Inbred C57BL
Retinal Pigment Epithelium*
Smoking* / adverse effects

Abstract

Publication types

MeSH terms

Grants and funding