EYS Mutations Causing Autosomal Recessive Retinitis Pigmentosa: Changes of Retinal Structure and Function with Disease Progression.

David Mcguigan,Monica Lu,Edwin Stone,Anand Swaroop,Rinki Ratnapriya,Samuel Jacobson,Artur Cideciyan,Alexandra Garafalo,Alexander Sumaroka,Vaishnavi Batmanabane,Alejandro Roman,Elise Heon

doi:10.3390/genes8070178

Abstract

Mutations in the EYS (eyes shut homolog) gene are a common cause of autosomal recessive (ar) retinitis pigmentosa (RP). Without a mammalian model of human EYS disease, there is limited understanding of details of disease expression and rates of progression of the retinal degeneration. We studied clinically and with chromatic static perimetry, spectral-domain optical coherence tomography (OCT), and en face autofluoresence imaging, a cohort of 15 patients (ages 12–51 at first visit), some of whom had longitudinal data of function and structure. Rod sensitivity was able to be measured by chromatic perimetry in most patients at their earliest visits and some patients retained patchy rod function into the fifth decade of life. As expected from RP, cone sensitivity persisted after rod function was no longer measurable. The photoreceptor nuclear layer of the central retina was abnormal except at the fovea in most patients at first visit. Perifoveal disease measured over a period of years indicated that photoreceptor structural loss was followed by dysmorphology of the inner retina and loss of retinal pigment epithelial integrity. Although there could be variability in severity, preliminary analyses of the rates of vision loss suggested that EYS is a more rapidly progressive disease than other ciliopathies causing arRP, such as USH2A and MAK.

Highlights

Understanding of disease expression in inherited retinal degenerations (IRDs) has benefited from in vitro studies, animal models that faithfully mimic the human condition, and histopathology of post-mortem retina donors
Missense mutations, truncating mutations, gross deletions and splice-site mutations were represented in this cohort, reflecting the diversity of mutations known to occur in this gene
How does EYS-retinitis pigmentosa (RP) compare with other ciliopathies causing arRP in terms of a time course of progression? Very few serial data of vision have been reported for EYS-RP [41]

Summary

Introduction

Understanding of disease expression in inherited retinal degenerations (IRDs) has benefited from in vitro studies, animal models that faithfully mimic the human condition, and histopathology of post-mortem retina donors. There were no cones in the peripheral retina; rhodopsin labeled cells were rare or absent in the analyzed areas (periphery and perifoveal regions); the perifovea was described as showing a prominent inner nuclear layer (INL) with patchy disorganized cones; and there were localized areas of retinal pigment epithelium (RPE) atrophy in the perifovea. Prompted by these clues about later-stage EYS disease, we studied a cohort of EYS-RP patients with non-invasive measures of photoreceptor function and structure and of RPE integrity. Many of our EYS-RP patients were able to be studied longitudinally and this provided a glimpse of the natural history of this relatively common form of arRP

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Conclusion