Abstract
BackgroundIn Leber's congenital amaurosis (LCA), affected individuals are blind, or nearly so, from birth. This early onset suggests abnormal development of the neural retina. Mutations in genes that affect the development and/or function of photoreceptor cells have been found to be responsible in some families. These examples include mutations in the photoreceptor transcription factor, Crx.ResultsA Crx mutant strain of mice was created to serve as a model for LCA and to provide more insight into Crx's function. In this study, an ultrastructural analysis of the developing retina in Crx mutant mice was performed. Outer segment morphogenesis was found to be blocked at the elongation stage, leading to a failure in production of the phototransduction apparatus. Further, Crx-/- photoreceptors demonstrated severely abnormal synaptic endings in the outer plexiform layer.ConclusionsThis is the first report of a synaptogenesis defect in an animal model for LCA. These data confirm the essential role this gene plays in multiple aspects of photoreceptor development and extend our understanding of the basic pathology of LCA.
Highlights
In Leber's congenital amaurosis (LCA), affected individuals are blind, or nearly so, from birth
At postnatal day 21 (P21), when Crx+/+ photoreceptors exhibited robust outer segments (Figure 1A, os), Crx-/- retinas were without a recognizable outer segment layer (Figure 1B)
Crx is necessary for the formation of photoreceptor terminals In a previous study, we demonstrated that forced expression of a dominant-negative allele of Crx in developing rods blocked formation of both rod spherules in the outer plexiform layer (OPL) and outer segments [7]
Summary
In Leber's congenital amaurosis (LCA), affected individuals are blind, or nearly so, from birth This early onset suggests abnormal development of the neural retina. Mutations in genes that affect the development and/or function of photoreceptor cells have been found to be responsible in some families. These examples include mutations in the photoreceptor transcription factor, Crx. Photoreceptor cells play a primary role in vision by capturing light energy and converting it into neural stimuli. Photoreceptor cells play a primary role in vision by capturing light energy and converting it into neural stimuli These sensory neurons are a shared element in all organisms capable of sensing light. Crx (conerod homeobox) is an otx-family homeobox gene expressed predominantly in photoreceptors, from early in (page number not for citation purposes)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
