{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T11:24:16Z","timestamp":1789125856221,"version":"build-2803163510"},"reference-count":59,"publisher":"American Society for Clinical Investigation","issue":"4","license":[{"start":{"date-parts":[[2022,2,22]],"date-time":"2022-02-22T00:00:00Z","timestamp":1645488000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"crossref","award":["R24EY027283,P30 014195,EY031566"],"award-info":[{"award-number":["R24EY027283,P30 014195,EY031566"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National instates of health general Medicine","award":["T32GM007250."],"award-info":[{"award-number":["T32GM007250."]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,2,22]]},"abstract":"<jats:p>\n                    Adiponectin receptor 1 (ADIPOR1) is a lipid and glucose metabolism regulator that possesses intrinsic ceramidase activity. Mutations of the\n                    <jats:italic>ADIPOR1<\/jats:italic>\n                    gene have been associated with nonsyndromic and syndromic retinitis pigmentosa. Here, we show that the absence of\n                    <jats:italic>AdipoR1<\/jats:italic>\n                    in mice leads to progressive photoreceptor degeneration, significant reduction of electroretinogram amplitudes, decreased retinoid content in the retina, and reduced cone opsin expression. Single-cell RNA-Seq results indicate that\n                    <jats:italic>ADIPOR1<\/jats:italic>\n                    encoded the most abundantly expressed ceramidase in mice and one of the 2 most highly expressed ceramidases in the human retina, next to acid ceramidase\n                    <jats:italic>ASAH1<\/jats:italic>\n                    . We discovered an accumulation of ceramides in the\n                    <jats:italic>\n                      AdipoR1\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    retina, likely due to insufficient ceramidase activity for healthy retina function, resulting in photoreceptor death. Combined treatment with desipramine\/L-cycloserine (DC) lowered ceramide levels and exerted a protective effect on photoreceptors in\n                    <jats:italic>\n                      AdipoR1\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    mice. Moreover, we observed improvement in cone-mediated retinal function in the DC-treated animals. Lastly, we found that prolonged DC treatment corrected the electrical responses of the primary visual cortex to visual stimuli, approaching near-normal levels for some parameters. These results highlight the importance of ADIPOR1 ceramidase in the retina and show that pharmacological inhibition of ceramide generation can provide a therapeutic strategy for\n                    <jats:italic>ADIPOR1-<\/jats:italic>\n                    related retinopathy.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.156301","type":"journal-article","created":{"date-parts":[[2022,1,11]],"date-time":"2022-01-11T13:11:30Z","timestamp":1641906690000},"source":"Crossref","is-referenced-by-count":49,"title":["Inhibition of ceramide accumulation in AdipoR1\u2013\/\u2013 mice increases photoreceptor survival and improves vision"],"prefix":"10.1172","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2233-5501","authenticated-orcid":true,"given":"Dominik","family":"Lewandowski","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Gavin Herbert Eye Institute, UCI, Irvine, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1110-9223","authenticated-orcid":true,"given":"Andrzej T.","family":"Foik","sequence":"additional","affiliation":[{"name":"International Center for Translational Eye Research, Institute of Physical Chemistry, Polish Academy of Sciences, Warsaw, Poland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roman","family":"Smidak","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Gavin Herbert Eye Institute, UCI, Irvine, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elliot H.","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Gavin Herbert Eye Institute, UCI, Irvine, California, USA."},{"name":"Medical Scientist Training Program, Case Western Reserve University, Cleveland, Ohio, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianye","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Gavin Herbert Eye Institute, UCI, Irvine, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thanh","family":"Hoang","sequence":"additional","affiliation":[{"name":"Solomon H. Snyder Department of Neuroscience, Johns Hopkins University, Baltimore, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3256-8990","authenticated-orcid":true,"given":"Aleksander","family":"Tworak","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Gavin Herbert Eye Institute, UCI, Irvine, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4921-1429","authenticated-orcid":true,"given":"Susie","family":"Suh","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Gavin Herbert Eye Institute, UCI, Irvine, California, USA."},{"name":"Medical Scientist Training Program, Case Western Reserve University, Cleveland, Ohio, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0388-832X","authenticated-orcid":true,"given":"Henri","family":"Leinonen","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Gavin Herbert Eye Institute, UCI, Irvine, California, USA."},{"name":"School of Pharmacy, University of Eastern Finland, Kuopio, Finland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8748-4532","authenticated-orcid":true,"given":"Zhiqian","family":"Dong","sequence":"additional","affiliation":[{"name":"Polgenix Inc., Department of Medical Devices, Cleveland Ohio, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2215-7653","authenticated-orcid":true,"given":"Antonio F.M.","family":"Pinto","sequence":"additional","affiliation":[{"name":"Clayton Foundation Laboratories for Peptide Biology, Salk Institute for Biological Studies, La Jolla, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1687-9948","authenticated-orcid":true,"given":"Emily","family":"Tom","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Gavin Herbert Eye Institute, UCI, Irvine, California, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennings","family":"Luu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Gavin Herbert Eye Institute, UCI, Irvine, California, USA."},{"name":"Medical Scientist Training Program, Case Western Reserve University, Cleveland, Ohio, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joan","family":"Lee","sequence":"additional","affiliation":[{"name":"MetroHealth Medical Center, Case Western Reserve University, Cleveland, Ohio, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuli","family":"Ma","sequence":"additional","affiliation":[{"name":"Polgenix Inc., Department of Medical Devices, Cleveland Ohio, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erhard","family":"Bieberich","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Kentucky, Lexington, Kentucky, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seth","family":"Blackshaw","sequence":"additional","affiliation":[{"name":"Solomon H. 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