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Histopathological comparison of eyes from patients with autosomal recessive retinitis pigmentosa caused by novel EYS mutations

  • Genetics
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Abstract

To evaluate the retinal histopathology in donor eyes from patients with autosomal recessive retinitis pigmentosa (arRP) caused by EYS mutations. Eyes from a 72-year-old female (donor 1, family 1), a 91-year-old female (donor 2, family 2), and her 97-year-old sister (donor 3, family 2) were evaluated with macroscopic, scanning laser ophthalmoscopy (SLO) and optical coherence tomography (OCT) imaging. Age-similar normal eyes and an eye donated by donor 1’s asymptomatic mother (donor 4, family 1) were used as controls. The perifovea and peripheral retina were processed for microscopy and immunocytochemistry with markers for cone and rod photoreceptor cells. DNA analysis revealed EYS mutations c.2259 + 1G > A and c.2620C > T (p.Q874X) in family 1, and c.4350_4356del (p.I1451Pfs*3) and c.2739-?_3244 + ?del in family 2. Imaging studies revealed the presence of bone spicule pigment in arRP donor retinas. Histology of all three affected donor eyes showed very thin retinas with little evidence of stratified nuclear layers in the periphery. In contrast, the perifovea displayed a prominent inner nuclear layer. Immunocytochemistry analysis demonstrated advanced retinal degenerative changes in all eyes, with near-total absence of rod photoreceptors. In addition, we found that the perifoveal cones were more preserved in retinas from the donor with the midsize genomic rearrangement (c.4350_4356del (p.I1451Pfs*3) and c.2739-?_3244 + ?del) than in retinas from the donors with the truncating (c.2259 + 1G > A and c.2620C > T (p.Q874X) mutations. Advanced retinal degenerative changes with near-total absence of rods and preservation of some perifoveal cones are observed in arRP donor retinas with EYS mutations.

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Acknowledgments

The authors thank Dr. Peter MacLeish (Morehouse School of Medicine, Atlanta, GA, USA) for providing us with the antibody to cone arrestin (7G6), and Xiaoping Yang for expert technical assistance. Supported by The Foundation Fighting Blindness Histopathology Grant F-OH01-1102-0231 (JGH), Research Center Grants from The Foundation Fighting Blindness (JGH), Research to Prevent Blindness Unrestricted Grant, The Llura and Gordon Gund Foundation, and National Institutes of Health grant R01EY014240-08 (JGH).

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Authors and Affiliations

  1. Ophthalmic Research - i31, Cleveland Clinic, Cole Eye Institute, 9500 Euclid Avenue, Cleveland, OH, 44195, USA

    Vera L. Bonilha, Mary E. Rayborn, Brent A. Bell, Meghan J. Marino, Gayle J. Pauer, Craig D. Beight, Elias I. Traboulsi, Joe G. Hollyfield & Stephanie A. Hagstrom

  2. Department of Ophthalmology, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, 44195, USA

    Vera L. Bonilha, Elias I. Traboulsi, Joe G. Hollyfield & Stephanie A. Hagstrom

  3. Casey Eye Institute, Portland, OR, 97239, USA

    John Chiang

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  1. Vera L. Bonilha
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Correspondence to Vera L. Bonilha.

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Bonilha, V.L., Rayborn, M.E., Bell, B.A. et al. Histopathological comparison of eyes from patients with autosomal recessive retinitis pigmentosa caused by novel EYS mutations. Graefes Arch Clin Exp Ophthalmol 253, 295–305 (2015). https://doi.org/10.1007/s00417-014-2868-z

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  • DOI: https://doi.org/10.1007/s00417-014-2868-z

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