An overview of leber congenital amaurosis: a model to understand human retinal development

  • Robert K Koenekoop
    Correspondence
    Reprint address: Robert Koenekoop, MD, PhD, FRCS, The Children's Vision Center and The McGill Ocular Genetics Laboratory at The Montreal Children's Hospital of McGill University, 2300 Tupper, Montreal PQ, Canada H3H 1P3.
    Affiliations
    McGill Ocular Genetics Laboratory, Montreal Children's Hospital, McGill University Health Center, Montreal, Quebec, Canada
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      Abstract

      Leber congenital amaurosis is a congenital retinal dystrophy described almost 150 years ago. Today, Leber congenital amaurosis is proving instrumental in our understanding of the molecular events that determine normal and aberrant retinal development. Six genes have been shown to be mutated in Leber congenital amaurosis, and they participate in a wide variety of retinal pathways: retinoid metabolism (RPE65), phototransduction (GUCY2D), photoreceptor outer segment development (CRX), disk morphogenesis (RPGRIP1), zonula adherens formation (CRB1), and cell-cycle progression (AIPL1). Longitudinal studies of visual performance show that most Leber congenital amaurosis patients remain stable, some deteriorate, and rare cases exhibit improvements. Histopathological analyses reveal that most cases have extensive degenerative retinal changes, some have an entirely normal retinal architecture, whereas others have primitive, poorly developed retinas. Animal models of Leber congenital amaurosis have greatly added to understanding the impact of the genetic defects on retinal cell death, and response to rescue. Gene therapy for RPE65 deficient dogs partially restored sight, and provides the first real hope of treatment for this devastating blinding condition.

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