Abstract
PurposeMutations in the EYS gene are a common cause of autosomal recessive retinitis pigmentosa (arRP), yet the role of the EYS protein in humans is presently unclear. The aim of this study was to investigate the isoform structure, expression and potential function of EYS in the mammalian retina in order to better understand its involvement in the pathogenesis of arRP.MethodsTo achieve the objective, we examined the expression of mRNA transcripts of EYS isoforms in human tissues and cell lines by RT-PCR. We also investigated the localisation of EYS in cultured cells and retinal cryo-sections by confocal fluorescence microscopy and Western blot analysis.ResultsRT-PCR analysis confirmed that EYS has at least four isoforms. In addition to the previously reported EYS isoforms 1 and 4, we present the experimental validation of two smaller variants referred to as EYS isoforms 2 and 3. All four isoforms are expressed in the human retina and Y79 cells and the short variants were additionally detected in the testis. Immunofluorescent confocal microscopy and Western blot analysis revealed that all EYS isoforms preferentially localise to the cytoplasm of Y79 and HeLa cells. Moreover, an enrichment of the endogenous protein was observed near the centrosomes in Y79 cells. Interestingly, EYS was observed at the ciliary axoneme in Y79 ciliated cells. In macaque retinal cryosections, EYS was found to localise in the region of the photoreceptor ciliary axoneme in both rods and cones as well as in the cytoplasm of the ganglion cells.ConclusionThe results obtained in this study lead us to speculate that, in photoreceptor cells, EYS could be a protein involved in maintaining the stability of the ciliary axoneme in both rods and cones. The variability of its isoform structure suggests that other roles are also possible and yet to be established.
Highlights
Retinitis pigmentosa (RP, OMIM #268000) is a heterogeneous group of inherited retinopathies characterised by progressive degeneration of photoreceptor cells leading to visual impairment and eventually to complete blindness [1]
In addition to the previously reported EYS isoforms 1 and 4, we present the experimental validation of two smaller variants referred to as EYS isoforms 2 and 3
The results obtained in this study lead us to speculate that, in photoreceptor cells, EYS could be a protein involved in maintaining the stability of the ciliary axoneme in both rods and cones
Summary
Retinitis pigmentosa (RP, OMIM #268000) is a heterogeneous group of inherited retinopathies characterised by progressive degeneration of photoreceptor cells leading to visual impairment and eventually to complete blindness [1]. Mutations in the EYS gene are the commonest cause of non-syndromic autosomal recessive retinitis pigmentosa (arRP; OMIM #602772) [3, 4]. The mutation prevalence ranges from 5% in the Dutch and Canadian populations [5] to 18–23.5% in the Japanese population [6], where mutations in EYS have emerged as the most frequent cause of inherited retinal dystrophies overall [7]. There has been a report of a Japanese individual diagnosed with cone-rod dystrophy caused by a compound heterozygous mutation in EYS [8]. It has been estimated that the visual field in patients with mutations in EYS begins to progressively deteriorate at around 30 years of age [9]
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