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http://purl.uniprot.org/citations/35616930http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/35616930http://www.w3.org/2000/01/rdf-schema#comment"

Purpose

Bietti crystalline dystrophy (BCD) is a progressive retinal degenerative disease primarily characterized by numerous crystal-like deposits and degeneration of retinal pigment epithelium (RPE) and photoreceptor cells. CYP4V2 (cytochrome P450 family 4 subfamily V member 2) is currently the only disease-causing gene for BCD. We aimed to generate a zebrafish model to explore the functional role of CYP4V2 in the development of BCD and identify potential therapeutic targets for future studies.

Methods

The cyp4v7 and cyp4v8 (homologous genes of CYP4V2) knockout zebrafish lines were generated by CRISPR/Cas9 technology. The morphology of photoreceptor and RPE cells and the accumulation of lipid droplets in RPE cells were investigated at a series of different developmental stages through histological analysis, immunofluorescence, and lipid staining. Transcriptome analysis was performed to investigate the changes in gene expression of RPE cells during the progression of BCD.

Results

Progressive retinal degeneration including RPE atrophy and photoreceptor loss was observed in the mutant zebrafish as early as seven months after fertilization. We also observed the excessive accumulation of lipid droplets in RPE cells from three months after fertilization, which preceded the retinal degeneration by several months. Transcriptome analysis suggested that multiple metabolism pathways, especially the lipid metabolism pathways, were significantly changed in RPE cells. The down-regulation of the peroxisome proliferator-activated receptor α (PPARα) pathway was further confirmed in the mutant zebrafish and CYP4V2-knockdown human RPE-1 cells.

Conclusions

Our work established an animal model that recapitulates the symptoms of BCD patients and revealed that abnormal lipid metabolism in RPE cells, probably caused by dysregulation of the PPARα pathway, might be the main and direct consequence of CYP4V2 deficiency. These findings will deepen our understanding of the pathogenesis of BCD and provide potential therapeutic approaches."xsd:string
http://purl.uniprot.org/citations/35616930http://purl.org/dc/terms/identifier"doi:10.1167/iovs.63.5.32"xsd:string
http://purl.uniprot.org/citations/35616930http://purl.uniprot.org/core/author"Chen X."xsd:string
http://purl.uniprot.org/citations/35616930http://purl.uniprot.org/core/author"Han Y."xsd:string
http://purl.uniprot.org/citations/35616930http://purl.uniprot.org/core/author"Huang Y."xsd:string
http://purl.uniprot.org/citations/35616930http://purl.uniprot.org/core/author"Hu H."xsd:string
http://purl.uniprot.org/citations/35616930http://purl.uniprot.org/core/author"Liu F."xsd:string
http://purl.uniprot.org/citations/35616930http://purl.uniprot.org/core/author"Liu M."xsd:string
http://purl.uniprot.org/citations/35616930http://purl.uniprot.org/core/author"Li P."xsd:string
http://purl.uniprot.org/citations/35616930http://purl.uniprot.org/core/author"Lv Y."xsd:string
http://purl.uniprot.org/citations/35616930http://purl.uniprot.org/core/author"Ren X."xsd:string
http://purl.uniprot.org/citations/35616930http://purl.uniprot.org/core/author"Tang Z."xsd:string
http://purl.uniprot.org/citations/35616930http://purl.uniprot.org/core/author"Wang Q."xsd:string
http://purl.uniprot.org/citations/35616930http://purl.uniprot.org/core/author"Zhang Z."xsd:string
http://purl.uniprot.org/citations/35616930http://purl.uniprot.org/core/author"Gao P."xsd:string
http://purl.uniprot.org/citations/35616930http://purl.uniprot.org/core/author"Jia D."xsd:string
http://purl.uniprot.org/citations/35616930http://purl.uniprot.org/core/author"Sun K."xsd:string
http://purl.uniprot.org/citations/35616930http://purl.uniprot.org/core/date"2022"xsd:gYear
http://purl.uniprot.org/citations/35616930http://purl.uniprot.org/core/name"Invest Ophthalmol Vis Sci"xsd:string
http://purl.uniprot.org/citations/35616930http://purl.uniprot.org/core/pages"32"xsd:string
http://purl.uniprot.org/citations/35616930http://purl.uniprot.org/core/title"Accumulation of Lipid Droplets in a Novel Bietti Crystalline Dystrophy Zebrafish Model With Impaired PPARalpha Pathway."xsd:string
http://purl.uniprot.org/citations/35616930http://purl.uniprot.org/core/volume"63"xsd:string
http://purl.uniprot.org/citations/35616930http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/35616930
http://purl.uniprot.org/citations/35616930http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/35616930
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