{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T04:09:28Z","timestamp":1747368568477,"version":"3.40.5"},"reference-count":56,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T00:00:00Z","timestamp":1747267200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100020595","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["NSTC 110-2320-B-040-022"],"award-info":[{"award-number":["NSTC 110-2320-B-040-022"]}],"id":[{"id":"10.13039\/100020595","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020595","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["NSTC 111-2813-C-040-027-B"],"award-info":[{"award-number":["NSTC 111-2813-C-040-027-B"]}],"id":[{"id":"10.13039\/100020595","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec020\">\n<jats:title>Background<\/jats:title>\n<jats:p><jats:italic>Klotho<\/jats:italic> mutation has been known to accelerate aging and degenerative pathogenesis, notably in the kidney and the brain. Nevertheless, the aftermath of <jats:italic>Klotho<\/jats:italic> function deprivation in the retina has not been detailed. This study aimed to provide an in-depth analysis of retinopathy caused by <jats:italic>Klotho<\/jats:italic> mutation.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec021\">\n<jats:title>Results<\/jats:title>\n<jats:p>The homozygous <jats:italic>Klotho<\/jats:italic> mutant mice retinas were analyzed at the 6<jats:sup>th<\/jats:sup>, 8<jats:sup>th<\/jats:sup> and 10<jats:sup>th<\/jats:sup> weeks of age, along with their heterozygous, and wild-type littermates between both genders. The electroretinogram results showed retinal function impairment with <jats:italic>Klotho<\/jats:italic> null mutation, as compared with their littermates. Nevertheless, there was no difference in the retinal layer thickness, morphology, and cell death up to 10 weeks of age among the three genotypes. No evident damage was detected in the photoreceptors, interneurons, and retinal ganglion cells with <jats:italic>Klotho<\/jats:italic> mutation up to 10 weeks of age. Amyloid-beta and hyperphosphorylated tau protein deposits were detected in the <jats:italic>Klotho<\/jats:italic> mutant retina, along with glial cell activation at 10 weeks of age.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec022\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>The results revealed that <jats:italic>Klotho<\/jats:italic> null mutation leads to retinal degeneration characterized by functional impairments, gliosis, and amyloid-beta and hyperphosphorylated tau protein deposition in the retina. Klotho protein function is, therefore, mandatory for the maintenance of a healthy retina. The mouse <jats:italic>Klotho<\/jats:italic> null mutation may be used as a study model for age-related retinal degeneration and Alzheimer\u2019s disease.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0323633","type":"journal-article","created":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T17:39:23Z","timestamp":1747330763000},"page":"e0323633","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Klotho null mutation leads to retinal degeneration characterized by functional impairment, gliosis, and deposition of amyloid-beta and hyperphosphorylated tau proteins"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-2317-5668","authenticated-orcid":true,"given":"Zhi-Jia","family":"Chen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chun-Yen","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fang-Yan","family":"Hsiao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing-Chun","family":"Ma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriel","family":"Lai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Han-Hsin","family":"Chang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David Pei-Cheng","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,5,15]]},"reference":[{"issue":"6655","key":"pone.0323633.ref001","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/36285","article-title":"Mutation of the mouse klotho gene leads to a syndrome resembling ageing","volume":"390","author":"M Kuro-o","year":"1997","journal-title":"Nature"},{"issue":"5742","key":"pone.0323633.ref002","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1126\/science.1112766","article-title":"Suppression of aging in mice by the hormone Klotho","volume":"309","author":"H Kurosu","year":"2005","journal-title":"Science"},{"issue":"41","key":"pone.0323633.ref003","doi-asserted-by":"crossref","first-page":"16346","DOI":"10.1523\/JNEUROSCI.0402-13.2013","article-title":"Klotho regulates retinal pigment epithelial functions and protects against oxidative 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