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

  • Vera L. BonilhaEmail author
  • Mary E. Rayborn
  • Brent A. Bell
  • Meghan J. Marino
  • Gayle J. Pauer
  • Craig D. Beight
  • John Chiang
  • Elias I. Traboulsi
  • Joe G. Hollyfield
  • Stephanie A. Hagstrom


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.


Recessive retinitis pigmentosa EYS mutations Histopathology Immunohistochemistry 



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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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Vera L. Bonilha
    • 1
    • 2
    Email author
  • Mary E. Rayborn
    • 1
  • Brent A. Bell
    • 1
  • Meghan J. Marino
    • 1
  • Gayle J. Pauer
    • 1
  • Craig D. Beight
    • 1
  • John Chiang
    • 3
  • Elias I. Traboulsi
    • 1
    • 2
  • Joe G. Hollyfield
    • 1
    • 2
  • Stephanie A. Hagstrom
    • 1
    • 2
  1. 1.Ophthalmic Research - i31, Cleveland ClinicCole Eye InstituteClevelandUSA
  2. 2.Department of OphthalmologyCleveland Clinic Lerner College of Medicine of Case Western Reserve UniversityClevelandUSA
  3. 3.Casey Eye InstitutePortlandUSA

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