title: Nature of the visual loss in observers with Leber's congenital amaurosis caused by specific mutations in RPE65.
abstract: OBJECTIVE
  To characterize visual losses associated with genetic mutations in the RPE65 gene that cause defects in the RPE-specific isomerase, RPE65. RPE65 is an important component of the retinoid cycle that restores 11-cis-retinal after its photoisomerization to its all-trans form. The defects investigated here cause Leber's congenital amaurosis (LCA2), an autosomal, recessively-inherited, severe, congenital-onset rod-cone dystrophy.
  
  
  METHODS
  Vision was assessed in nine patients and 10 normal controls by measuring: (1) long-wavelength sensitive (L-) cone temporal acuity (critical flicker fusion frequency or cff) as a function of target illuminance, and (2) L-cone temporal contrast sensitivity as a function of temporal frequency at a fixed-target illuminance. Measurements were made by modulating either a 650-nm light superimposed on a 480-nm background or the red phosphor of a color monitor on a background produced by the monitor's blue phosphor.
  
  
  RESULTS
  RPE65-mutant observers have severely reduced cffs with shallower cff versus log illuminance functions that rise with a mean slope of 4.53 Hz per decade of illuminance compared with 8.69 Hz in normal controls. Consistent with the cff differences, RPE65-mutant observers show losses in temporal contrast sensitivity that increase rapidly with temporal frequency.
  
  
  CONCLUSIONS
  All RPE65-mutant observers have consistent and substantial losses in temporal acuity and sensitivity compared with normal observers. The losses can be characterized by the addition of two sluggish filters within the mutant visual pathway, both filters with a time constant of 29.5 ms (i.e., low-pass filters with cut-off frequencies of 5.40 Hz).
authors.affiliation: UCL Institute of Ophthalmology, University College London, London, England.
authors.forename: Caterina
authors.initials: C
authors.lastname: Ripamonti
authors.affiliation: UCL Institute of Ophthalmology, University College London, London, England.
authors.forename: G Bruce
authors.initials: GB
authors.lastname: Henning
authors.affiliation: UCL Institute of Ophthalmology, University College London, London, England.
authors.forename: Robin R
authors.initials: RR
authors.lastname: Ali
authors.affiliation: UCL Institute of Ophthalmology, University College London, London, England.
authors.forename: James W
authors.initials: JW
authors.lastname: Bainbridge
authors.affiliation: UCL Institute of Ophthalmology, University College London, London, England.
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Robbie
authors.affiliation: UCL Institute of Ophthalmology, University College London, London, England.
authors.forename: Venki
authors.initials: V
authors.lastname: Sundaram
authors.affiliation: UCL Institute of Ophthalmology, University College London, London, England.
authors.forename: Vy A
authors.initials: VA
authors.lastname: Luong
authors.affiliation: Rotterdam Eye Hospital, Rotterdam, The Netherlands.
authors.forename: L Ingeborgh
authors.initials: LI
authors.lastname: van den Born
authors.affiliation: Department of Ophthalmology, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Ingele
authors.initials: I
authors.lastname: Casteels
authors.affiliation: Centre for Human Genetics, University Hospitals Leuven, Belgium.
authors.forename: Thomy J L
authors.initials: TJ
authors.lastname: de Ravel
authors.affiliation: UCL Institute of Ophthalmology, University College London, London, England.
authors.forename: Anthony T
authors.initials: AT
authors.lastname: Moore
authors.affiliation: UCL Institute of Ophthalmology, University College London, London, England.
authors.forename: Andrew
authors.initials: A
authors.lastname: Stockman
mesh_terms: D000293:Adolescent; D000328:Adult; D001766:Blindness / Q000201:enzymology / Q000209:etiology / Q000235:genetics*; D002648:Child; D015350:Contrast Sensitivity; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005425:Flicker Fusion; D006801:Humans; D057130:Leber Congenital Amaurosis / Q000150:complications* / Q000201:enzymology / Q000235:genetics; D008297:Male; D009154:Mutation; D010775:Photic Stimulation; D017949:Retinal Cone Photoreceptor Cells / Q000201:enzymology* / Q000473:pathology; D055815:Young Adult; D019745:cis-trans-Isomerases / Q000235:genetics* / Q000378:metabolism; D000099178:Retinoid Isomerohydrolase
chemical_list: D004247:DNA; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase
keywords: LCA2; Leber's congenital amaurosis; RPE65; flicker sensitivity; rods and cones; scotopic; temporal processing