{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T08:56:39Z","timestamp":1773651399964,"version":"3.50.1"},"reference-count":34,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,2,16]],"date-time":"2025-02-16T00:00:00Z","timestamp":1739664000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,2,16]],"date-time":"2025-02-16T00:00:00Z","timestamp":1739664000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100021704","name":"Czech Centre for Phenogenomics, Institute of Molecular Genetics of the Czech Academy of Sciences","doi-asserted-by":"publisher","award":["RVO 68378050"],"award-info":[{"award-number":["RVO 68378050"]}],"id":[{"id":"10.13039\/501100021704","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005310","name":"Claire and Am\u00e9d\u00e9e Maratier Institute for the Study of Blindness and Visual Disorders, Tel Aviv University","doi-asserted-by":"publisher","award":["0601412281"],"award-info":[{"award-number":["0601412281"]}],"id":[{"id":"10.13039\/501100005310","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Exper Ophthalmology"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      This study investigates the role of the\n                      <jats:italic>SLC38A8<\/jats:italic>\n                      gene.\n                      <jats:italic>SLC38A8<\/jats:italic>\n                      facilitates glutamine influx, which converts to glutamate in the visual pathway. Mutations in\n                      <jats:italic>SLC38A8<\/jats:italic>\n                      are associated with FHONDA syndrome, a subtype of foveal hypoplasia with congenital nystagmus and optic\u2010nerve\u2010decussation defects without pigmentation leading to severe vision loss.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In vivo and in\u00a0vitro methods were conducted using retinal cell lines overexpressing\n                      <jats:italic>SLC38A8<\/jats:italic>\n                      , and\n                      <jats:italic>Slc38a8<\/jats:italic>\n                      \/\n                      <jats:italic>Slc38a7<\/jats:italic>\n                      gene\u2010edited mice to evaluate visual function and physiological changes. Statistical analyses included two\u2010way ANOVA, multiple regression, and ANCOVA.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In vitro,\n                      <jats:italic>SLC38A8<\/jats:italic>\n                      overexpression influenced retinal gene expression, light detection, and visual perception, as well as glutamine and glutamate dynamics. In Y79\n                      <jats:sup>SNAT8\u2010OE<\/jats:sup>\n                      cells, glutamate levels were significantly higher under light conditions compared to dark conditions at 12\u2009h (3.4\u2009\u00b1\u20090.16\u2009nmol\/\u03bcl vs. 3.9\u2009\u00b1\u20090.17\u2009nmol\/\u03bcl,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0011) and 17\u2009h (3.6\u2009\u00b1\u20090.22\u2009nmol\/\u03bcl vs. 4.5\u2009\u00b1\u20090.24\u2009nmol\/\u03bcl,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0001), a pattern not observed in control cells.\n                      <jats:italic>SLC38A8<\/jats:italic>\n                      expression also increased significantly (RQ\u2009=\u20092.1\u2009\u00b1\u20090.11,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05) in Y79 cells under glutamine deprivation. In\u00a0vivo,\n                      <jats:italic>Slc38a8<\/jats:italic>\n                      \u2010truncated gene mice exhibited altered testicular morphology, with significantly reduced volume (70.9\u2009\u00b1\u20095.1\u2009mm\n                      <jats:sup>3<\/jats:sup>\n                      vs. 85.5\u2009\u00b1\u20096.7\u2009mm\n                      <jats:sup>3<\/jats:sup>\n                      ,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.023), and reduced length (4.8\u2009\u00b1\u20090.2\u2009mm vs. 5.4\u2009\u00b1\u20090.4\u2009mm,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0169), alongside degenerative changes in germinal epithelium, and elevated liver enzyme. Despite normal eye morphology, retinal thickness, and visual evoked potentials, electroretinogram and behavioural tests indicated enhanced scotopic responsiveness with significant increases in a\u2010wave (162.98\u2009\u00b1\u200914.1\u2009\u03bcv vs. 133.9\u2009\u00b1\u200936.9\u2009\u03bcv,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20091.5e\u201007) and b\u2010wave amplitudes (274.82\u2009\u00b1\u200925.2\u2009\u03bcv vs. 199.9\u2009\u00b1\u200956.1\u2009\u03bcv,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20093.02e\u201009).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Our findings underscore\n                      <jats:italic>SLC38A8<\/jats:italic>\n                      role in retinal function and glutamine\u2010glutamate metabolism, with clinical implications for FHONDA and potential future dietary intervention targeting glutamine or glutamate.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/ceo.14504","type":"journal-article","created":{"date-parts":[[2025,2,16]],"date-time":"2025-02-16T22:00:06Z","timestamp":1739743206000},"page":"542-557","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Characterisation of\n                    <i>SLC38A8<\/i>\n                    and Its Role in Retinal Pathways and Disease"],"prefix":"10.1111","volume":"53","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6186-0379","authenticated-orcid":false,"given":"Chen","family":"Weiner","sequence":"first","affiliation":[{"name":"Matlow Ophthalmo\u2010Genetic Laboratory, Department of Ophthalmology Shamir Medical Centre  Tzrifin Israel"},{"name":"Faculty of Medicine Tel Aviv University  Tel Aviv Israel"},{"name":"Clinical Laboratory 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