Journal article
Interleukin-17 retinotoxicity is prevented by gene transfer of a soluble interleukin-17 receptor acting as a cytokine blocker: implications for age-related macular degeneration
PloS one, Vol.9(4), pp.e95900-e95900
2014
DOI: 10.1371/journal.pone.0095900
PMCID: PMC4004582
PMID: 24780906
Abstract
Age-related macular degeneration (AMD) is a common yet complex retinal degeneration that causes irreversible central blindness in the elderly. Pathology is widely believed to follow loss of retinal pigment epithelium (RPE) and photoreceptor degeneration. Here we report aberrant expression of interleukin-17A (IL17A) and the receptor IL17RC in the macula of AMD patients. In vitro, IL17A induces RPE cell death characterized by the accumulation of cytoplasmic lipids and autophagosomes with subsequent activation of pro-apoptotic Caspase-3 and Caspase-9. This pathology is reduced by siRNA knockdown of IL17RC. IL17-dependent retinal degeneration in a mouse model of focal retinal degeneration can be prevented by gene therapy with adeno-associated virus vector encoding soluble IL17 receptor. This intervention rescues RPE and photoreceptors in a MAPK-dependent process. The IL17 pathway plays a key role in RPE and photoreceptor degeneration and could hold therapeutic potential in AMD.
Details
- Title: Subtitle
- Interleukin-17 retinotoxicity is prevented by gene transfer of a soluble interleukin-17 receptor acting as a cytokine blocker: implications for age-related macular degeneration
- Creators
- Daniel Ardeljan - Immunopathology Section, Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States of America; School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of AmericaYujuan Wang - National Institutes of HealthStanley Park - National Institutes of HealthDefen Shen - Immunopathology Section, Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States of AmericaXi Kathy Chu - Immunopathology Section, Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States of AmericaCheng-Rong Yu - Molecular Immunology Section, Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States of AmericaMones Abu-Asab - Histology Core, Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States of AmericaJingsheng Tuo - Immunopathology Section, Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States of AmericaCharles G Eberhart - Department of Pathology, Johns Hopkins University, Baltimore, Maryland, United States of AmericaTimothy W Olsen - Department of Ophthalmology, Emory University, Atlanta, Georgia, United States of AmericaRobert F Mullins - Department of Ophthalmology and Visual Sciences, University of Iowa Carver College of Medicine, Iowa City, Iowa, United States of AmericaGary White - Genzyme Corporation, Framingham, Massachusetts, United States of AmericaSam Wadsworth - Genzyme Corporation, Framingham, Massachusetts, United States of AmericaAbraham Scaria - Genzyme Corporation, Framingham, Massachusetts, United States of AmericaChi-Chao Chan - Immunopathology Section, Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States of America
- Resource Type
- Journal article
- Publication Details
- PloS one, Vol.9(4), pp.e95900-e95900
- DOI
- 10.1371/journal.pone.0095900
- PMID
- 24780906
- PMCID
- PMC4004582
- NLM abbreviation
- PLoS One
- ISSN
- 1932-6203
- eISSN
- 1932-6203
- Publisher
- United States
- Language
- English
- Date published
- 2014
- Academic Unit
- Ophthalmology and Visual Sciences
- Record Identifier
- 9983980077602771
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