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

• DOI: 10.1371/journal.pone.0095900
• Publication Date: 2014-04-29T20:15:56Z
• Authors: 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
• Keywords: Receptors, Interleukin-17; Science; Q; Genetic Vectors; Interleukin-17; R; Dependovirus; Transfection; Retina; 3. Good health; Macular Degeneration; 03 medical and health sciences; 0302 clinical medicine; Medicine; Cytokines; Humans; Research Article

Age-related macular degeneration (AMD) is a common yet complex retinal that causes irreversible central blindness in the elderly. Pathology widely believed to follow loss of pigment epithelium (RPE) and photoreceptor degeneration. Here we report aberrant expression interleukin-17A (IL17A) receptor IL17RC macula AMD patients. In vitro, IL17A induces RPE cell death characterized by accumulation cytoplasmic lipids autophagosomes with subsequent activation pro-apoptotic Caspase-3 Caspase-9. This pathology reduced siRNA knockdown IL17RC. IL17-dependent mouse model focal can be prevented gene therapy adeno-associated virus vector encoding soluble IL17 receptor. intervention rescues photoreceptors MAPK-dependent process. The pathway plays key role could hold therapeutic potential AMD.