Type 2a usher syndrome11/29/2023 Congressional Testimony and the NIDCD Budget.Research Training in NIDCD Laboratories (Intramural).Types of Research Training Funding Opportunities.About NIDCD's Research Training Program.Scientific Workshop and Meeting Reports.Building a Diverse Scientific Workforce.Al-Ubaidi, Moores Professor of biomedical engineering Lars Tebbe, assistant professor of research Mustafa Makia and three students recently graduated: Maggie Mwoyosvi, Ryan Crane and Mashal Kakakhel. Others on the Naash team at UH include Muayyad R. "Our model exhibits retinal degeneration associated with a decline in retinal function and continues to support the development of an effective gene therapy platform to treat USH2A associated visual defects," said Naash. Because the model closely mimics the disease it will allow Naash to study the mechanism of the disease and investigate options for treatment including gene therapy. Those results prove that expression of the actual mutant protein is beneficial in reproducing USH2A retinal phenotype and offers insight into strategies for designing therapeutic interventions.Īn in-depth analysis of the retina in the model revealed structural anomalies in the photoreceptors ultimately leading to the death of the photoreceptor cells causing vision loss. The degeneration is associated with a decline in retinal function, structural abnormalities in connecting cilium and outer segment and mislocalization of the usherin interacting partners-very long G-protein receptor 1 (VLGR1) and whirlin (WHRN)." "The model exhibits retinal degeneration and expresses a truncated, glycosylated protein which is mislocalized to the photoreceptor inner segment. Dunn Endowed Professor of Biomedical Engineering. "In our study, published in Nature Communications, we designed and generated a model expressing c.2299delG, the most common human disease mutation in USH2A," reports Muna Naash, John S. Most Usher syndrome models successfully reproduce the hearing loss observed in patients but fail to model the visual problems. Currently no treatment exists for USH2A.Īlso, no study has come close to examining the actual mechanics behind the illness, until now-even though establishing a model for USH2A that mirrors patient's phenotypes has been an important goal for the future development of therapeutic strategies. RP affects the retina, the eye's light-sensitive layer, leading to a breakdown of the light-sensitive cells in the retina which initially leads to night blindness followed by progressive loss of daily vision. USH2A, caused by mutations in the USH2A gene, can include hearing loss from birth and progressive loss of vision, prompting retinitis pigmentosa (RP). Usher syndrome, a rare inherited genetic disease, is a leading cause of combined deafness and blindness with type 2A (USH2A) being the most common form. PMC periciliary membrane complex, OS outer segment, IS inner segment, Rho rhodopsin, ER endoplasmic reticulum, CC connecting cilium. Additionally, a huge portion of the mutant usherin is trapped in the ER, causing cellular stress. The disruption of the PMC decreases the loading efficacy of rhodopsin in the CC and thus impacts its transport toward the OS. WHRN is mislocalized towards the OS and inner segment. WHRN and VLGR1 are trapped in the inner segment in vesicles, no longer able to localize at the ciliary pocket. B In the Ush2a delG/delG photoreceptor, the PMC is disrupted. A In the WT photoreceptor cells, the PMC is intact, facilitating the efficient loading of cargo, including rhodopsin, into the CC. Schematic summarizing the role of mutant usherin in impacting the structure of the periciliary membrane complex.
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