PUBLICATION
Transcriptome alterations in sf3b4-depleted zebrafish: Insights into cataract formation in retinitis pigmentosa model
- Authors
- Ulhaq, Z.S., Ogino, Y., Tse, W.K.F.
- ID
- ZDB-PUB-240205-5
- Date
- 2024
- Source
- Experimental Eye Research 240: 109819 (Journal)
- Registered Authors
- Ulhaq, Zulvikar Syambani
- Keywords
- Cytokines, Inflammation, Lens opacification, TGF-β, Transcriptomic
- MeSH Terms
-
- Animals
- Capsule Opacification*/etiology
- Cataract*/etiology
- Crystallins*/genetics
- Humans
- Lens, Crystalline*
- Retinitis Pigmentosa*/diagnosis
- Retinitis Pigmentosa*/genetics
- Transcriptome
- Zebrafish/genetics
- PubMed
- 38311285 Full text @ Exp. Eye. Res.
Citation
Ulhaq, Z.S., Ogino, Y., Tse, W.K.F. (2024) Transcriptome alterations in sf3b4-depleted zebrafish: Insights into cataract formation in retinitis pigmentosa model. Experimental Eye Research. 240:109819.
Abstract
Posterior subcapsular cataract (PSC) frequently develops as a complication in patients with retinitis pigmentosa (RP). Despite numerous scientific investigations, the intricate pathomechanisms underlying cataract formation in individuals affected by RP remain elusive. Therefore, our study aims to elucidate the potential pathogenesis of cataracts in an RP model using splicing factor subunit 3b (sf3b4) mutant zebrafish. By analyzing our previously published transcriptome dataset, we identified that, in addition to RP, cataract was listed as the second condition in our transcriptomic analysis. Furthermore, we confirmed the presence of nucleus retention in the lens fiber cells, along with abnormal cytoskeleton expression in both the lens fiber cells and lens epithelial cells in sf3b4-depleted fish. Upon closer examination, we identified 20 differentially expressed genes (DEGs) that played a role in cataract fo rmation, with 95 % of them related to the downregulation of structural lens proteins. Additionally, we also identifed that among all the DEGs, 13 % were associated with fibrotic processes. It seems that the significant upregulation of inflammatory mediators, in conjunction with TGF-β signaling, plays a central role in the cellular biology of PSC and posterior capsular opacification (PCO) in sf3b4 mutant fish. In summary, our study provides valuable insights into cataract formation in the RP model of sf3b4 mutants, highlighting its complexity driven by changes in structural lens proteins and increased cytokines/growth factors.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping