Ablation of EYS in zebrafish causes mislocalisation of outer segment proteins, F-actin disruption and cone-rod dystrophy

• Published in: Scientific reports 2017-04, Vol.7 (1), p.46098-46098, Article 46098
• Main Authors: Lu, Zhaojing, Hu, Xuebin, Liu, Fei, Soares, Dinesh C., Liu, Xiliang, Yu, Shanshan, Gao, Meng, Han, Shanshan, Qin, Yayun, Li, Chang, Jiang, Tao, Luo, Daji, Guo, An-Yuan, Tang, Zhaohui, Liu, Mugen
• Format: Article
• Language: English
• Subjects: 13/2; 14/19; 14/28; 14/34; 38/23; 38/77; 631/208/135; 631/378/2613/1786; Actin; Actins - metabolism; Aging - pathology; Animals; Apoptosis; Base Sequence; Cone-Rod Dystrophies - metabolism; Cone-Rod Dystrophies - pathology; Cone-Rod Dystrophies - physiopathology; Cones; Dystrophy; Electroretinography; Eye Proteins - metabolism; Filaments; Gene Deletion; Gene Knockout Techniques; Humanities and Social Sciences; Immunofluorescence; Light Signal Transduction; Molecular modelling; multidisciplinary; Mutation; Photoreceptors; Protein transport; Retina; Retinal degeneration; Retinitis; Retinitis pigmentosa; Rhodopsin; Rod Cell Outer Segment - metabolism; Rod Cell Outer Segment - pathology; Rod Cell Outer Segment - ultrastructure; Rod outer segment membranes; Rods; Science; Transcription Activator-Like Effector Nucleases - metabolism; Vision, Ocular; Visual perception; Zebrafish - metabolism; Zebrafish Proteins - metabolism
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep46098

Mutations in EYS are associated with autosomal recessive retinitis pigmentosa (arRP) and autosomal recessive cone-rod dystrophy (arCRD) however, the function of EYS and the molecular mechanisms of how these mutations cause retinal degeneration are still unclear. Because EYS is absent in mouse and rat, and the structure of the retina differs substantially between humans and Drosophila , we utilised zebrafish as a model organism to study the function of EYS in the retina. We constructed an EYS -knockout zebrafish-line by TALEN technology which showed visual impairment at an early age, while the histological and immunofluorescence assays indicated the presence of progressive retinal degeneration with a cone predominately affected pattern. These phenotypes recapitulate the clinical manifestations of arCRD patients. Furthermore, the EYS −/− zebrafish also showed mislocalisation of certain outer segment proteins (rhodopsin, opn1lw, opn1sw1, GNB3 and PRPH2), and disruption of actin filaments in photoreceptors. Protein mislocalisation may, therefore, disrupt the function of cones and rods in these zebrafish and cause photoreceptor death. Collectively, these results point to a novel role for EYS in maintaining the morphological structure of F-actin and in protein transport, loss of this function might be the trigger for the resultant cellular events that ultimately lead to photoreceptor death.