RegulomeDB score of 13 SNPs of <i>CNTNAP5</i>.

<div><p>Primary angle closure glaucoma (PACG) affects more than 20 million people worldwide, with an increased prevalence in south-east Asia. In a prior haplotype-based Genome Wide Association Study (GWAS), we identified a novel <i>CNTNAP5</i> genic region, significantly associated with PACG. In the current study, we have extended our perception of <i>CNTNAP5</i> involvement in glaucomatous neurodegeneration in a zebrafish model, through investigating phenotypic consequences pertinent to retinal degeneration upon knockdown of <i>cntnap5</i> by translation-blocking morpholinos. While <i>cntnap5</i> knockdown was successfully validated using an antibody, immunofluorescence followed by western blot analyses in cntnap5-morphant (MO) zebrafish revealed increased expression of acetylated tubulin indicative of perturbed cytoarchitecture of retinal layers. Moreover, significant loss of Nissl substance is observed in the neuro-retinal layers of cntnap5-MO zebrafish eye, indicating neurodegeneration. Additionally, in spontaneous movement behavioural analysis, cntnap5-MO zebrafish have a significantly lower average distance traversed in light phase compared to mismatch-controls, whereas no significant difference was observed in the dark phase, corroborating with vision loss in the cntnap5-MO zebrafish. This study provides the first direct functional evidence of a putative role of <i>CNTNAP5</i> in visual neurodegeneration.</p></div>