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In a prior haplotype-based Genome Wide Association Study (GWAS), we identified a novel <jats:italic>CNTNAP5<\/jats:italic> genic region, significantly associated with PACG. In the current study, we have extended our perception of <jats:italic>CNTNAP5<\/jats:italic> involvement in glaucomatous neurodegeneration in a zebrafish model, through investigating phenotypic consequences pertinent to retinal degeneration upon knockdown of <jats:italic>cntnap5<\/jats:italic> by translation-blocking morpholinos. While <jats:italic>cntnap5<\/jats:italic> 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 <jats:italic>CNTNAP5<\/jats:italic> in visual neurodegeneration.<\/jats:p>","DOI":"10.1371\/journal.pgen.1011502","type":"journal-article","created":{"date-parts":[[2024,12,5]],"date-time":"2024-12-05T19:25:03Z","timestamp":1733426703000},"page":"e1011502","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Functional investigation suggests CNTNAP5 involvement in glaucomatous neurodegeneration obtained from a GWAS in primary angle closure glaucoma"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2277-9759","authenticated-orcid":true,"given":"Sudipta","family":"Chakraborty","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jyotishman","family":"Sarma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shantanu Saha","family":"Roy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sukanya","family":"Mitra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sayani","family":"Bagchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0768-6862","authenticated-orcid":true,"given":"Sankhadip","family":"Das","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sreemoyee","family":"Saha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Surajit","family":"Mahapatra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8549-1130","authenticated-orcid":true,"given":"Samsiddhi","family":"Bhattacharjee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9046-3716","authenticated-orcid":true,"given":"Mahua","family":"Maulik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8013-7426","authenticated-orcid":true,"given":"Moulinath","family":"Acharya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,12,5]]},"reference":[{"key":"pgen.1011502.ref001","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1136\/bjo.2005.081224","article-title":"The number of people with glaucoma worldwide in 2010 and 2020","volume":"90","author":"HA Quigley","year":"2006","journal-title":"Br J Ophthalmol"},{"key":"pgen.1011502.ref002","doi-asserted-by":"crossref","first-page":"1901","DOI":"10.1001\/jama.2014.3192","article-title":"The pathophysiology and treatment of glaucoma: a review","volume":"311","author":"RN Weinreb","year":"2014","journal-title":"JAMA"},{"key":"pgen.1011502.ref003","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1007\/s12041-021-01321-2","article-title":"A genomewide association study on individuals with occludable angles identifies potential risk loci for intraocular pressure","volume":"100","author":"S Chakraborty","year":"2021","journal-title":"J Genet"},{"key":"pgen.1011502.ref004","doi-asserted-by":"crossref","first-page":"R139","DOI":"10.1093\/hmg\/ddx273","article-title":"Optic neuropathies: the tip of the neurodegeneration iceberg","volume":"26","author":"V Carelli","year":"2017","journal-title":"Hum Mol Genet"},{"key":"pgen.1011502.ref005","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1136\/bjo.54.3.161","article-title":"Aetiology of the anatomical basis for primary angle-closure glaucoma. 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