title: Postretinal Structure and Function in Severe Congenital Photoreceptor Blindness Caused by Mutations in the GUCY2D Gene.
abstract: To examine how severe congenital blindness resulting from mutations of the GUCY2D gene alters brain structure and function, and to relate these findings to the notable preservation of retinal architecture in this form of Leber congenital amaurosis (LCA).
  
  
  
  Six GUCY2D-LCA patients (ages 20-46) were studied with optical coherence tomography of the retina and multimodal magnetic resonance imaging (MRI) of the brain. Measurements from this group were compared to those obtained from populations of normally sighted controls and people with congenital blindness of a variety of causes.
  
  
  
  Patients with GUCY2D-LCA had preservation of the photoreceptors, ganglion cells, and nerve fiber layer. Despite this, visual function in these patients ranged from 20/160 acuity to no light perception, and functional MRI responses to light stimulation were attenuated and restricted. This severe visual impairment was reflected in substantial thickening of the gray matter layer of area V1, accompanied by an alteration of resting-state correlations within the occipital lobe, similar to a comparison group of congenitally blind people with structural damage to the retina. In contrast to the comparison blind population, however, the GUCY2D-LCA group had preservation of the size of the optic chiasm, and the fractional anisotropy of the optic radiations as measured with diffusion tensor imaging was also normal.
  
  
  
  These results identify dissociable effects of blindness upon the visual pathway. Further, the relatively intact postgeniculate white matter pathway in GUCY2D-LCA is encouraging for the prospect of recovery of visual function with gene augmentation therapy.
authors.affiliation: Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States.
authors.forename: Geoffrey K
authors.initials: GK
authors.lastname: Aguirre
authors.affiliation: Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States.
authors.forename: Omar H
authors.initials: OH
authors.lastname: Butt
authors.affiliation: Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States.
authors.forename: Ritobrato
authors.initials: R
authors.lastname: Datta
authors.affiliation: Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States.
authors.forename: Alejandro J
authors.initials: AJ
authors.lastname: Roman
authors.affiliation: Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States.
authors.forename: Alexander
authors.initials: A
authors.lastname: Sumaroka
authors.affiliation: Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States.
authors.forename: Sharon B
authors.initials: SB
authors.lastname: Schwartz
authors.affiliation: Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States.
authors.forename: Artur V
authors.initials: AV
authors.lastname: Cideciyan
authors.affiliation: Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States.
authors.forename: Samuel G
authors.initials: SG
authors.lastname: Jacobson
mesh_terms: D000328:Adult; D001921:Brain / Q000503:physiopathology*; D056324:Diffusion Tensor Imaging; D005260:Female; D006162:Guanylate Cyclase / Q000235:genetics*; D006801:Humans; D057130:Leber Congenital Amaurosis / Q000235:genetics* / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009412:Nerve Fibers / Q000473:pathology; D009897:Optic Chiasm / Q000502:physiology; D010775:Photic Stimulation; D020419:Photoreceptor Cells, Vertebrate / Q000473:pathology*; D011956:Receptors, Cell Surface / Q000235:genetics*; D012165:Retinal Ganglion Cells / Q000473:pathology; D041623:Tomography, Optical Coherence; D014792:Visual Acuity / Q000502:physiology; D014795:Visual Pathways / Q000503:physiopathology; D055815:Young Adult
chemical_list: D011956:Receptors, Cell Surface; C110715:guanylate cyclase 1; D006162:Guanylate Cyclase