title: Human retinal disease from AIPL1 gene mutations: foveal cone loss with minimal macular photoreceptors and rod function remaining.
abstract: OBJECTIVE
  To determine the human retinal phenotype caused by mutations in the gene encoding AIPL1 (Aryl hydrocarbon receptor-interacting protein-like 1) now that there are proof-of-concept results for gene therapy success in Aipl1-deficient mice.
  
  
  METHODS
  Leber congenital amaurosis (LCA) patients (n = 10) and one patient with a later-onset retinal degeneration (RD) and AIPL1 mutations were studied by ocular examination, retinal imaging, perimetry, full-field sensitivity testing, and pupillometry.
  
  
  RESULTS
  The LCA patients had severe visual acuity loss early in life, nondetectable electroretinograms (ERGs), and little or no detectable visual fields. Hallmarks of retinal degeneration were present in a wide region, including the macula and midperiphery; there was some apparent peripheral retinal sparing. Cross-sectional imaging showed foveal cone photoreceptor loss with a ring of minimally preserved paracentral photoreceptor nuclear layer. Features of retinal remodeling were present eccentric to the region of detectable photoreceptors. Full-field sensitivity was reduced by at least 2 log units, and chromatic stimuli, by psychophysics and pupillometry, revealed retained but impaired rod function. The RD patient, examined serially over two decades (ages, 45-67 years), retained an ERG in the fifth decade of life with abnormal rod and cone signals; and there was progressive loss of central and peripheral function.
  
  
  CONCLUSIONS
  AIPL1-LCA, unlike some other forms of LCA with equally severe visual disturbance, shows profound loss of foveal as well as extrafoveal photoreceptors. The more unusual late-onset and slower form of AIPL1 disease may be better suited to gene augmentation therapy and is worthy of detection and further study.
authors: Department of Ophthalmology, University of Pennsylvania, Philadelphia, PA, USA. jacobsos@mail.med.upenn.edu
authors: Samuel G
authors: SG
authors: Jacobson
authors: Artur V
authors: AV
authors: Cideciyan
authors: Tomas S
authors: TS
authors: Aleman
authors: Alexander
authors: A
authors: Sumaroka
authors: Alejandro J
authors: AJ
authors: Roman
authors: Malgorzata
authors: M
authors: Swider
authors: Sharon B
authors: SB
authors: Schwartz
authors: Eyal
authors: E
authors: Banin
authors: Edwin M
authors: EM
authors: Stone
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000293:Adolescent; D000328:Adult; D000368:Aged; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004596:Electroretinography; D005136:Eye Proteins; D005260:Female; D005584:Fovea Centralis / Q000473:pathology*; D006801:Humans; D007223:Infant; D057130:Leber Congenital Amaurosis / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D011680:Pupil / Q000502:physiology; D017949:Retinal Cone Photoreceptor Cells / Q000473:pathology*; D012162:Retinal Degeneration / Q000235:genetics* / Q000503:physiopathology; D017948:Retinal Rod Photoreceptor Cells / Q000473:pathology*; D041623:Tomography, Optical Coherence; D014792:Visual Acuity / Q000502:physiology; D058609:Visual Field Tests; D014794:Visual Fields / Q000502:physiology; D055815:Young Adult
chemical_list: C403625:AIPL1 protein, human; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D005136:Eye Proteins