期刊
GENE
卷 892, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.gene.2023.147885
关键词
Retinitis pigmentosa; USH2A; Zebrafish; Vesicle transport; Pathogenesis
USH2A gene mutations are the main cause of Usher syndrome type 2 and non-syndromic RP. This study investigated the pathological mechanisms of RP using a zebrafish model and found that the knockout of ush2a may affect vesicle transport, leading to structural and functional damage of photoreceptor cells.
USH2A (Usher syndrome type 2A) gene mutations are the predominant cause of Usher syndrome type 2, char-acterized by sensorineural hearing loss and retinitis pigmentosa (RP), and also significant contributors to non-syndromic RP. To date, there is a lack of definitive therapeutic interventions to mitigate the associated disor-ders caused by USH2A mutations, and the precise pathogenic mechanisms underlying their onset remain unclear. In the present study, we utilized the ush2a knockout zebrafish model to investigate the pathological mechanisms of RP. In late-stage ush2a-/-zebrafish, the outer segments of rods displayed shortened length and decreased number. Anomalous vesicle accumulation was observed at the junction between the inner and outer segments, accompanied by reduced expression and structural damage of actin filaments in the photoreceptor cells. Furthermore, we discovered that Rab8 expression was downregulated and exhibited aberrant localization in ush2a-/-zebrafish. Additionally, we identified an interaction between USH2A and Rab8. Therefore, the knockout of ush2a may potentially affect vesicle transport through the regulation of Rab8, providing a novel target for maintaining the survival of photoreceptor cells. These findings also contribute to our understanding of the potential molecular pathogenesis underlying RP caused by USH2A gene mutations.
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