Find in Library

Inherited retinal degenerations (IRDs) are a group of genetic disorders characterized by the progressive degeneration of retinal cells, leading to irreversible vision loss. <i>SLC4A7</i> has emerged as a candidate gene associated with IRDs, yet its mechanisms remain largely unknown. This study aims to investigate the role of <i>slc4a7</i> in retinal development and its associated molecular pathogenesis in zebrafish. Morpholino oligonucleotide knockdown, CRISPR/Cas9 genome editing, quantitative RT-PCR, eye morphometric measurements, immunofluorescent staining, TUNEL assays, visual motor responses, optokinetic responses, rescue experiments, and bulk RNA sequencing were used to assess the impact of <i>slc4a7</i> deficiency on retinal development. Our results demonstrated that the knockdown of <i>slc4a7</i> resulted in a dose-dependent reduction in eye axial length, ocular area, and eye-to-body-length ratio. The fluorescence observations showed a significant decrease in immunofluorescence signals from photoreceptors and in mCherry fluorescence from RPE in <i>slc4a7</i>-silenced morphants. TUNEL staining uncovered the extensive apoptosis of retinal cells induced by slc4a7 knockdown. Visual behaviors were significantly impaired in the <i>slc4a7</i>-deficient larvae. GO and KEGG pathway analyses reveal that differentially expressed genes are predominantly linked to aspects of vision, ion channels, and phototransduction. This study demonstrates that the loss of <i>slc4a7</i> in larvae led to profound visual impairments, providing additional insights into the genetic mechanisms predisposing individuals to IRDs caused by <i>SLC4A7</i> deficiency.