Interleukin-17 Retinotoxicity Is Prevented by Gene Transfer of a Soluble Interleukin-17 Receptor Acting as a Cytokine Blocker: Implications for Age-Related Macular DegenerationReportar como inadecuado




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 - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

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.



Autor: Daniel Ardeljan, Yujuan Wang, Stanley Park, Defen Shen, Xi Kathy Chu, Cheng-Rong Yu, Mones Abu-Asab, Jingsheng Tuo, Charles G. Eb

Fuente: http://plos.srce.hr/



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