title: Spectral sensitivity measurements reveal partial success in restoring missing rod function with gene therapy.
abstract: Restored rod visual function after gene therapy can be established unequivocally by demonstrating that, after dark adaptation, spectral sensitivity has the shape characteristic of rods and that this shape collapses to a cone-like shape before rods have recovered after an intense bleach. We used these tests to assess retinal function in eight young adults and children with early-onset severe retinal dystrophy from Phase II of a clinical gene-therapy trial for RPE65 deficiency that involved the subretinal delivery of a recombinant adeno-associated viral vector carrying RPE65. We found substantial improvements in rod sensitivity in two participants: dark-adapted spectral sensitivity was rod-like after treatment and was cone-like before rods had recovered after a bleach. After 40 min of dark adaptation, one participant showed up to 1,000-fold sensitivity improvements 4 months after treatment and the second up to 100-fold improvements 6 months after treatment. The dark-adapted spectral sensitivities of the other six participants remained cone-like and showed little improvement in sensitivity.
authors.forename: Caterina
authors.initials: C
authors.lastname: Ripamonti
authors.forename: G Bruce
authors.initials: GB
authors.lastname: Henning
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Robbie
authors.forename: Venki
authors.initials: V
authors.lastname: Sundaram
authors.forename: L Ingeborgh
authors.initials: LI
authors.lastname: van den Born
authors.forename: Ingele
authors.initials: I
authors.lastname: Casteels
authors.forename: Thomy J L
authors.initials: TJ
authors.lastname: de Ravel
authors.forename: Anthony T
authors.initials: AT
authors.lastname: Moore
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Smith
authors.forename: James W
authors.initials: JW
authors.lastname: Bainbridge
authors.forename: Robin R
authors.initials: RR
authors.lastname: Ali
authors.forename: Andrew
authors.initials: A
authors.lastname: Stockman
mesh_terms: D000328:Adult; D002648:Child; D003623:Dark Adaptation / Q000502:physiology; D000229:Dependovirus / Q000235:genetics*; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D057130:Leber Congenital Amaurosis / Q000503:physiopathology* / Q000628:therapy*; D008027:Light; D008875:Middle Aged; D010775:Photic Stimulation; D017948:Retinal Rod Photoreceptor Cells / Q000502:physiology*; D014785:Vision, Ocular / Q000502:physiology*; D014792:Visual Acuity / Q000502:physiology; D014794:Visual Fields / Q000502:physiology; D055815:Young Adult; D019745:cis-trans-Isomerases / Q000235:genetics*; D000099178:Retinoid Isomerohydrolase
chemical_list: D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase