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Abstract #118603 Published in IGR 24-4
Post-GWAS functional analyses of suggests its role in glaucomatous neurodegeneration
Chakraborty S; Sarma J; Roy SS; Mitra S; Bagchi S; Das S; Saha S; Mahapatra S; Bhattacharjee S; Maulik M; Acharya MbioRxiv : the preprint server for biology 2024; 0:
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 GWAS, we identified a novel genic region, significantly associated with PACG. In the current study, we have extended our perception of involvement in glaucomatous neurodegeneration in a zebrafish model, through investigating phenotypic consequences pertinent to retinal degeneration upon knockdown of cntnap5 by translation-blocking morpholinos. While cntnap5 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 in visual neurodegeneration.
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