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To gain novel insight into its normal function, we used transposon-mediated transgenesis to generate the first zebrafish line stably overexpressing myocilin [Tg(actb1:myoc-2A-mCherry)]. qPCR showed an approximately four-fold increased myocilin expression in transgenic zebrafish embryos (144 hpf). Adult (13 months old) transgenic animals displayed variable and age-dependent ocular anterior segment alterations. Almost 60% of two-year-old male, but not female, transgenic zebrafish developed enlarged eyes with severe asymmetrical and variable abnormalities in the anterior segment, characterized by corneal limbus hypertrophy, and thickening of the cornea, iris, annular ligament and lens capsule. The most severe phenotype presented small or absent ocular anterior chamber and pupils, due to iris overgrowth along with dysplastic retinal growth and optic nerve hypertrophy. Immunohistochemistry revealed increased presence of myocilin in most altered ocular tissues of adult transgenic animals, as well as signs of retinal gliosis and expanded ganglion cells and nerve fibers. The preliminary results indicate that these cells contributed to retinal dysplasia. Visual impairment was demonstrated in all old male transgenic zebrafish. Transcriptomic analysis of the abnormal transgenic eyes identified disrupted expression of genes involved in lens, muscular and extracellular matrix activities, among other processes. In summary, the developed transgenic zebrafish provides a new tool to investigate this puzzling protein and provides evidence for the role of zebrafish myocilin in ocular anterior segment and retinal biology, through the influence of extracellular matrix organization and cellular proliferation.<\/jats:p>","DOI":"10.3390\/ijms23179989","type":"journal-article","created":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T21:27:17Z","timestamp":1662067637000},"page":"9989","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Transgenic Overexpression of Myocilin Leads to Variable Ocular Anterior Segment and Retinal Alterations Associated with Extracellular Matrix Abnormalities in Adult Zebrafish"],"prefix":"10.3390","volume":"23","author":[{"given":"Raquel","family":"Atienzar-Aroca","sequence":"first","affiliation":[{"name":"\u00c1rea de Gen\u00e9tica, Facultad de Medicina de Albacete, Universidad de Castilla-La Mancha, 02006 Albacete, Spain"},{"name":"Instituto de Investigaci\u00f3n en Discapacidades Neurol\u00f3gicas (IDINE), Universidad de Castilla-La Mancha, 02006 Albacete, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9511-2894","authenticated-orcid":false,"given":"Jes\u00fas-Jos\u00e9","family":"Ferre-Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"\u00c1rea de Gen\u00e9tica, Facultad de Medicina de Albacete, Universidad de Castilla-La Mancha, 02006 Albacete, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angel","family":"Tevar","sequence":"additional","affiliation":[{"name":"\u00c1rea de Gen\u00e9tica, Facultad de Medicina de Albacete, Universidad de Castilla-La Mancha, 02006 Albacete, Spain"},{"name":"Instituto de Investigaci\u00f3n en Discapacidades Neurol\u00f3gicas (IDINE), Universidad de Castilla-La Mancha, 02006 Albacete, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan-Manuel","family":"Bonet-Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"\u00c1rea de Gen\u00e9tica, Facultad de Medicina de Albacete, Universidad de Castilla-La Mancha, 02006 Albacete, Spain"},{"name":"Instituto de Investigaci\u00f3n en Discapacidades Neurol\u00f3gicas (IDINE), Universidad de Castilla-La Mancha, 02006 Albacete, Spain"},{"name":"Cooperative Research Network on Age-Related Ocular Pathology, Visual and Life Quality (OFTARED), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda-Jos\u00e9","family":"Caba\u00f1ero","sequence":"additional","affiliation":[{"name":"\u00c1rea de Gen\u00e9tica, Facultad de Medicina de Albacete, Universidad de Castilla-La Mancha, 02006 Albacete, Spain"},{"name":"Instituto de Investigaci\u00f3n en Discapacidades Neurol\u00f3gicas (IDINE), Universidad de Castilla-La Mancha, 02006 Albacete, Spain"},{"name":"Cooperative Research Network on Age-Related Ocular Pathology, Visual and Life Quality (OFTARED), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda-Jos\u00e9","family":"Ruiz-Pastor","sequence":"additional","affiliation":[{"name":"Cooperative Research Network on Age-Related Ocular Pathology, Visual and Life Quality (OFTARED), Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Department of Physiology, Genetics and Microbiology, University of Alicante, 03080 Alicante, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6767-5710","authenticated-orcid":false,"given":"Nicol\u00e1s","family":"Cuenca","sequence":"additional","affiliation":[{"name":"Cooperative Research Network on Age-Related Ocular Pathology, Visual and Life Quality (OFTARED), Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Department of Physiology, Genetics and Microbiology, University of Alicante, 03080 Alicante, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6487-1612","authenticated-orcid":false,"given":"Jos\u00e9-Daniel","family":"Aroca-Aguilar","sequence":"additional","affiliation":[{"name":"\u00c1rea de Gen\u00e9tica, Facultad de Medicina de Albacete, Universidad de Castilla-La Mancha, 02006 Albacete, Spain"},{"name":"Instituto de Investigaci\u00f3n en Discapacidades Neurol\u00f3gicas (IDINE), Universidad de Castilla-La Mancha, 02006 Albacete, Spain"},{"name":"Cooperative Research Network on Age-Related Ocular Pathology, Visual and Life Quality (OFTARED), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8919-8134","authenticated-orcid":false,"given":"Julio","family":"Escribano","sequence":"additional","affiliation":[{"name":"\u00c1rea de Gen\u00e9tica, Facultad de Medicina de Albacete, Universidad de Castilla-La Mancha, 02006 Albacete, Spain"},{"name":"Instituto de Investigaci\u00f3n en Discapacidades Neurol\u00f3gicas (IDINE), Universidad de Castilla-La Mancha, 02006 Albacete, Spain"},{"name":"Cooperative Research Network on Age-Related Ocular Pathology, Visual and Life Quality (OFTARED), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1111\/j.1442-9071.1995.tb00135.x","article-title":"Ganglion cell death in glaucoma: Pathology recapitulates ontogeny","volume":"23","author":"Quigley","year":"1995","journal-title":"Aust. 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