title: Histopathology and functional correlations in a patient with a mutation in RPE65, the gene for retinol isomerase.
abstract: OBJECTIVE
  Here the authors describe the structural features of the retina and retinal pigment epithelium (RPE) in postmortem donor eyes of a 56-year-old patient with a homozygous missense RPE65 mutation (Ala132Thr) and correlate the pathology with the patient's visual function last measured at age 51.
  
  
  METHODS
  Eyes were enucleated within 13.5 hours after death. Representative areas from the macula and periphery were processed for light and electron microscopy. Immunofluorescence was used to localize the distribution of RPE65, rhodopsin, and cone arrestin. The autofluorescence in the RPE was compared with that of two normal eyes from age-similar donors.
  
  
  RESULTS
  Histologic examination revealed the loss of rods and cones across most areas of the retina, attenuated retinal vessels, and RPE thinning in both eyes. A small number of highly disorganized cones were present in the macula that showed simultaneous labeling with cone arrestin and red/green or blue opsin. RPE65 immunoreactivity and RPE autofluorescence were reduced compared with control eyes in all areas studied. Rhodopsin labeling was observed in rods in the far periphery. The optic nerve showed a reduced number of axons.
  
  
  CONCLUSIONS
  The clinical findings of reduced visual acuity, constricted fields, and reduced electroretinograms (ERGs) 5 years before death correlated with the small number of cones present in the macula and the extensive loss of photoreceptors in the periphery. The absence of autofluorescence in the RPE suggests that photoreceptor cells were probably missing across the retina for extended periods of time. Possible mechanisms that could lead to photoreceptor cell death are discussed.
authors.affiliation: Cole Eye Institute, Department of Ophthalmology, Cleveland Clinic Lerner College of Medicine, Cleveland, Ohio 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: Yong
authors.initials: Y
authors.lastname: Li
authors.forename: Gregory H
authors.initials: GH
authors.lastname: Grossman
authors.forename: Eliot L
authors.initials: EL
authors.lastname: Berson
authors.forename: Joe G
authors.initials: JG
authors.lastname: Hollyfield
mesh_terms: D019393:Arrestin / Q000378:metabolism; D016570:Bruch Membrane / Q000378:metabolism / Q000648:ultrastructure; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D004596:Electroretinography; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D009900:Optic Nerve / Q000473:pathology; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism / Q000648:ultrastructure; D012162:Retinal Degeneration / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D055213:Retinal Pigment Epithelium / Q000378:metabolism / Q000648:ultrastructure; D012243:Rhodopsin / Q000378:metabolism; D014786:Vision Disorders / Q000235:genetics / Q000503:physiopathology; D014792:Visual Acuity / Q000502:physiology; D014794:Visual Fields / Q000502:physiology; D019745:cis-trans-Isomerases / Q000235:genetics*; D000099178:Retinoid Isomerohydrolase
chemical_list: D019393:Arrestin; D002352:Carrier Proteins; D005136:Eye Proteins; D012243:Rhodopsin; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase; C077124:retinal isomerase