Nature of the visual loss in observers with Leber's congenital amaurosis caused by specific mutations in RPE65.
PURPOSE
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).
['Ripamonti|Caterina|C|', 'Henning|G Bruce|GB|', 'Ali|Robin R|RR|', 'Bainbridge|James W|JW|', 'Robbie|Scott J|SJ|', 'Sundaram|Venki|V|', 'Luong|Vy A|VA|', 'van den Born|L Ingeborgh|LI|', 'Casteels|Ingele|I|', 'de Ravel|Thomy J L|TJ|', 'Moore|Anthony T|AT|', 'Stockman|Andrew|A|']
D000293:Adolescent D000328:Adult D001766:Blindness D002648:Child D015350:Contrast Sensitivity D004247:DNA D004252:DNA Mutational Analysis D005260:Female D005425:Flicker Fusion D006801:Humans D057130:Leber Congenital Amaurosis D008297:Male D009154:Mutation D010775:Photic Stimulation D017949:Retinal Cone Photoreceptor Cells D055815:Young Adult D019745:cis-trans-Isomerases
Leber's congenital amaurosis RPE65 LCA2 flicker sensitivity rods and cones scotopic temporal processing