title: Retinal histopathology in eyes from patients with autosomal dominant retinitis pigmentosa caused by rhodopsin mutations.
abstract: OBJECTIVE
  To evaluate the histopathology in donor eyes from patients with autosomal dominant retinitis pigmentosa (ADRP) caused by p.P23H, p.P347T and p.P347L rhodopsin ( RHO ) gene mutations.
  
  
  METHODS
  Eyes from a 72-year-old male (donor 1), an 83-year-old female (donor 2), an 80-year-old female (donor 3), and three age-similar normal eyes were examined macroscopically, by scanning laser ophthalmoscopy and optical coherence tomography imaging. Perifoveal and peripheral pieces were processed for microscopy and immunocytochemistry with markers for photoreceptor cells.
  
  
  RESULTS
  DNA analysis revealed RHO mutations c.68C>A (p.P23H) in donor 1, c.1040C>T (p.P347L) in donor 2 and c.1039C>A (p.P347T) in donor 3. Histology of the ADRP eyes showed retinas with little evidence of stratified nuclear layers in the periphery and a prominent inner nuclear layer present in the perifoveal region in the p.P23H and p.P347T eyes, while it was severely atrophic in the p.P347L eye. The p.P23H and p.P347T mutations cause a profound loss of rods in both the periphery and perifovea, while the p.P347L mutation displays near complete absence of rods in both regions. All three rhodopsin mutations caused a profound loss of cones in the periphery. The p.P23H and p.P347T mutations led to the presence of highly disorganized cones in the perifovea. However, the p.P347L mutation led to near complete absence of cones also in the perifovea.
  
  
  CONCLUSIONS
  Our results support clinical findings indicating that mutations affecting residue P347 develop more severe phenotypes than those affecting P23. Furthermore, our results indicate a more severe phenotype in the p.P347L retina as compared to the p.P347T retina.
authors.affiliation: Cole Eye Institute, Cleveland Clinic, Ophthalmic Research - i31, 9500 Euclid Avenue, Cleveland, OH, 44195, USA. bonilhav@ccf.org.|Department of Ophthalmology, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, 44195, USA. bonilhav@ccf.org.
authors.forename: Vera L
authors.initials: VL
authors.lastname: Bonilha
authors.affiliation: Cole Eye Institute, Cleveland Clinic, Ophthalmic Research - i31, 9500 Euclid Avenue, Cleveland, OH, 44195, USA.
authors.forename: Mary E
authors.initials: ME
authors.lastname: Rayborn
authors.affiliation: Cole Eye Institute, Cleveland Clinic, Ophthalmic Research - i31, 9500 Euclid Avenue, Cleveland, OH, 44195, USA.
authors.forename: Brent A
authors.initials: BA
authors.lastname: Bell
authors.affiliation: Cole Eye Institute, Cleveland Clinic, Ophthalmic Research - i31, 9500 Euclid Avenue, Cleveland, OH, 44195, USA.
authors.forename: Meghan J
authors.initials: MJ
authors.lastname: Marino
authors.affiliation: Cole Eye Institute, Cleveland Clinic, Ophthalmic Research - i31, 9500 Euclid Avenue, Cleveland, OH, 44195, USA.
authors.forename: Craig D
authors.initials: CD
authors.lastname: Beight
authors.affiliation: Cole Eye Institute, Cleveland Clinic, Ophthalmic Research - i31, 9500 Euclid Avenue, Cleveland, OH, 44195, USA.
authors.forename: Gayle J
authors.initials: GJ
authors.lastname: Pauer
authors.affiliation: Cole Eye Institute, Cleveland Clinic, Ophthalmic Research - i31, 9500 Euclid Avenue, Cleveland, OH, 44195, USA.|Department of Ophthalmology, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, 44195, USA.
authors.forename: Elias I
authors.initials: EI
authors.lastname: Traboulsi
authors.affiliation: Cole Eye Institute, Cleveland Clinic, Ophthalmic Research - i31, 9500 Euclid Avenue, Cleveland, OH, 44195, USA.|Department of Ophthalmology, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, 44195, USA.
authors.forename: Joe G
authors.initials: JG
authors.lastname: Hollyfield
authors.affiliation: Cole Eye Institute, Cleveland Clinic, Ophthalmic Research - i31, 9500 Euclid Avenue, Cleveland, OH, 44195, USA.|Department of Ophthalmology, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, 44195, USA.
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Hagstrom
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D019393:Arrestin / Q000378:metabolism; D004596:Electroretinography; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009887:Ophthalmoscopy; D010375:Pedigree; D017354:Point Mutation; D017949:Retinal Cone Photoreceptor Cells / Q000378:metabolism / Q000473:pathology*; D017948:Retinal Rod Photoreceptor Cells / Q000378:metabolism / Q000473:pathology*; D012174:Retinitis Pigmentosa / Q000235:genetics* / Q000473:pathology*; D012243:Rhodopsin / Q000235:genetics* / Q000378:metabolism; D017299:Rod Opsins / Q000378:metabolism; D014019:Tissue Donors; D041623:Tomography, Optical Coherence
chemical_list: D019393:Arrestin; D017299:Rod Opsins; C095855:long-wavelength opsin; C095854:middle-wavelength opsin; D012243:Rhodopsin
keywords: Histopathology; Immunohistochemistry; Photoreceptors; Retinitis pigmentosa; Rhodopsin mutations