title: Histopathological comparison of eyes from patients with autosomal recessive retinitis pigmentosa caused by novel EYS mutations.
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.
authors.affiliation: Ophthalmic Research - i31, Cleveland Clinic, Cole Eye Institute, 9500 Euclid Avenue, Cleveland, OH, 44195, USA, bonilhav@ccf.org.
authors.forename: Vera L
authors.initials: VL
authors.lastname: Bonilha
authors.forename: Mary E
authors.initials: ME
authors.lastname: Rayborn
authors.forename: Brent A
authors.initials: BA
authors.lastname: Bell
authors.forename: Meghan J
authors.initials: MJ
authors.lastname: Marino
authors.forename: Gayle J
authors.initials: GJ
authors.lastname: Pauer
authors.forename: Craig D
authors.initials: CD
authors.lastname: Beight
authors.forename: John
authors.initials: J
authors.lastname: Chiang
authors.forename: Elias I
authors.initials: EI
authors.lastname: Traboulsi
authors.forename: Joe G
authors.initials: JG
authors.lastname: Hollyfield
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Hagstrom
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D004252:DNA Mutational Analysis; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D009154:Mutation; D009693:Nucleic Acid Hybridization; D009887:Ophthalmoscopy; D010375:Pedigree; D016133:Polymerase Chain Reaction; D012174:Retinitis Pigmentosa / Q000235:genetics* / Q000473:pathology*; D014019:Tissue Donors; D041623:Tomography, Optical Coherence
chemical_list: C533105:EYS protein, human; D005136:Eye Proteins