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

Daniel Ardeljan, Yujuan Wang, Stanley Park, Defen Shen, Xi Kathy Chu, Cheng Rong Yu, Mones Abu-Asab, Jingsheng Tuo, Charles G. Eberhart, Timothy W. Olsen, Robert F. Mullins, Gary White, Sam Wadsworth, Abraham Scaria, Chi Chao Chan

Research output: Contribution to journalArticle

22 Scopus citations

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.

Original languageEnglish (US)
Article numbere95900
JournalPloS one
Volume9
Issue number4
DOIs
StatePublished - Apr 29 2014

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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    Ardeljan, D., Wang, Y., Park, S., Shen, D., Chu, X. K., Yu, C. R., Abu-Asab, M., Tuo, J., Eberhart, C. G., Olsen, T. W., Mullins, R. F., White, G., Wadsworth, S., Scaria, A., & Chan, C. C. (2014). 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, 9(4), [e95900]. https://doi.org/10.1371/journal.pone.0095900