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.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 24780906.
- Also identified by DOI 10.1371/journal.pone.0095900 and PMC identifier 4004582.
- Licence recorded as CC0.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- Cytokines
- Interleukin-17
- Macular Degeneration
- Receptors, Interleukin-17
- Retina
- Transfection