A frameshift mutation in @entity72383 exon ORF15 causes @entity528 and XXXX in a model of @entity8105 .

@entity2000 @entity235 @entity8105 @entity990 @entity6391 @entity389 @entity989 @entity4334 @entity528 @entity72383
PURPOSE: To characterize the course of @entity989 in @entity989 ( @entity989 ), a @entity235 model of early onset @entity8105 ( @entity8105 ) caused by a two- @entity4334 microdeletion in @entity72383 ORF15. METHODS: The retinas of 25 @entity989 -affected @entity235 (age range, 2-40.6 weeks) and age-matched control subjects were collected, fixed, and embedded in @entity990 resin for morphologic evaluation or in optimal cutting temperature (OCT) medium for TUNEL assay and immunohistochemistry. Cell-specific antibodies were used to examine changes in rods and cones and to evaluate the effects of the primary @entity528 on inner retinal cells. RESULTS: Abnormal development of photoreceptors was recognizable as early as 3.9 weeks of age. Outer segment (OS) misalignment was followed by their disorganization and fragmentation. Reduction in length and broadening of rod and cone inner segments (IS) was next observed, followed by the focal loss of rod and cone IS at later time points. The proportion of dying photoreceptors peaked at approximately 6 to 7 weeks of age and was significantly reduced after 12 weeks. In addition to rod and cone opsin mislocalization, there was early rod neurite sprouting, retraction of rod bipolar cell dendrites, and increased M  ller cell reactivity. Later in the course of the disease, changes were also noted in horizontal cells and amacrine cells. CONCLUSIONS: @entity989 is an early-onset model of @entity8105 that is morphologically characterized by abnormal photoreceptor maturation followed by progressive @entity6391 and early @entity389 . The results suggest that therapeutic strategies for this @entity2000 should target not solely photoreceptor cells but also inner retinal neurons.
