XXXX : animal models, retinal function of Usher proteins, and prospects for gene therapy.

@entity1018 @entity1 @entity2000 @entity19 @entity39575 @entity15439 @entity1939 @entity2319 @entity389
@entity15439 is a @entity1018 . The @entity1939 occurs from a progressive @entity2000 that begins after @entity2319 and after the retina has developed. Three clinical subtypes of @entity15439 have been identified, with mutations in any one of six different genes giving rise to type 1, in any one of three different genes to type 2, and in one identified gene causing Usher type 3. Mutant @entity19 for most of the genes have been studied; while they have clear @entity389 , retinal phenotypes are relatively mild and have been difficult to characterize. The retinal functions of the Usher proteins are still largely unknown. Protein binding studies have suggested many interactions among the proteins, and a model of interaction among all the proteins in the photoreceptor synapse has been proposed. However this model is not supported by localization data from some laboratories, or the indication of any synaptic phenotype in mutant @entity19 . An earlier suggestion, based on @entity1 pathologies, of Usher protein function in the photoreceptor cilium continues to gain support from immunolocalization and mutant @entity19 studies, which are consistent with Usher protein interaction in the photoreceptor ciliary/periciliary region. So far, the most characterized Usher protein is @entity39575 . It is present in the apical RPE and photoreceptor ciliary/periciliary region, where it is required for organelle transport and clearance of opsin from the connecting cilium, respectively. @entity15439 is amenable to gene replacement therapy, but also has some specific challenges. Progress in this treatment approach has been achieved by correction of mutant phenotypes in @entity39575 -null @entity19 retinas, following lentiviral delivery of @entity39575 .
