Abstract
ABSTRACTMutations in the extracellular matrix protein eyes shut homolog (EYS) cause photoreceptor degeneration in patients with retinitis pigmentosa 25 (RP25). Functions of EYS remain poorly understood, due in part to the lack of an EYS gene in mouse. We investigated the localization of vertebrate EYS proteins and engineered loss-of-function alleles in zebrafish. Immunostaining indicated that EYS localized near the connecting cilium/transition zone in photoreceptors. EYS also strongly localized to the cone outer segments and weakly to the rod outer segments and cone terminals in primate retinas. Analysis of mutant EYS zebrafish revealed disruption of the ciliary pocket in cone photoreceptors, indicating that EYS is required for maintaining the integrity of the ciliary pocket lumen. Mutant zebrafish exhibited progressive loss of cone and rod photoreceptors. Our results indicate that EYS protein localization is species-dependent and that EYS is required for maintaining ciliary pocket morphology and survival of photoreceptors in zebrafish.
Highlights
Retinitis pigmentosa (OMIM #268000) is a heterogeneous group of genetic diseases exhibiting progressive retinal degeneration due to loss of photoreceptors
eyes shut homolog (EYS) protein is located near connecting cilium/transition zone (CC/TZ) in zebrafish retina To determine the distribution of the EYS protein in the zebrafish retina, we carried out immunofluorescence staining with an EYS antibody (Fig. 1)
Double staining with peanut agglutinin (PNA) (Fig. 1E, arrows) indicated that some EYS immunoreactive puncta were located on the basal end of PNA-positive outer segments
Summary
Retinitis pigmentosa (OMIM #268000) is a heterogeneous group of genetic diseases exhibiting progressive retinal degeneration due to loss of photoreceptors. It has a worldwide prevalence of 1/3000 to 1/7000. The autosomal recessive retinitis pigmentosa 25 (RP25, OMIM #612424) is caused by abnormal EYS (Abd El-Aziz et al, 2008; Collin et al, 2008), a secreted extracellular matrix protein, in several populations worldwide (Abd El-Aziz et al, 2008, 2010; Audo et al, 2010; Bandah-Rozenfeld et al, 2010; Barragán et al, 2010; Chen et al, 2015; Collin et al, 2008; Di et al, 2016; Hosono et al, 2012; Littink et al, 2010b). Mutations in EYS account for 5-16% of all autosomal recessive cases in Europe
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