{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T11:20:20Z","timestamp":1787570420359,"version":"build-2736575974"},"reference-count":41,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2024,5,10]],"date-time":"2024-05-10T00:00:00Z","timestamp":1715299200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,5,10]],"date-time":"2024-05-10T00:00:00Z","timestamp":1715299200000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,5,10]],"date-time":"2024-05-10T00:00:00Z","timestamp":1715299200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["K99EY030951"],"award-info":[{"award-number":["K99EY030951"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000011","name":"Howard Hughes Medical Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000011","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Lingang Laboratory","award":["Start up fund"],"award-info":[{"award-number":["Start up fund"]}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>\n                    Retinitis pigmentosa (RP) is an inherited retinal disease in which there is a loss of cone-mediated daylight vision. As there are &gt;100 disease genes, our goal is to preserve cone vision in a disease gene-agnostic manner. Previously we showed that overexpressing TXNIP, an \u03b1-arrestin protein, prolonged cone vision in RP mouse models, using an AAV to express it only in cones. Here, we expressed different alleles of\n                    <jats:italic>Txnip<\/jats:italic>\n                    in the retinal pigmented epithelium (RPE), a support layer for cones. Our goal was to learn more of TXNIP\u2019s structure-function relationships for cone survival, as well as determine the optimal cell type expression pattern for cone survival. The C-terminal half of TXNIP was found to be sufficient to remove GLUT1 from the cell surface, and improved RP cone survival, when expressed in the RPE, but not in cones. Knock-down of HSP90AB1, a TXNIP-interactor which regulates metabolism, improved the survival of cones alone and was additive for cone survival when combined with TXNIP. From these and other results, it is likely that TXNIP interacts with several proteins in the RPE to indirectly support cone survival, with some of these interactions different from those that lead to cone survival when expressed only in cones.\n                  <\/jats:p>","DOI":"10.7554\/elife.90749","type":"journal-article","created":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T10:06:35Z","timestamp":1694772395000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.90749","source":"Crossref","is-referenced-by-count":6,"title":["Txnip deletions and missense alleles prolong the survival of cones in a retinitis pigmentosa mouse model"],"prefix":"10.7554","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2088-9826","authenticated-orcid":true,"given":"Yunlu","family":"Xue","sequence":"first","affiliation":[{"name":"Departments of Genetics and Ophthalmology, Blavatnik Institute, Harvard Medical School","place":["Boston, United States"]},{"name":"Lingang Laboratory","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Yimin","family":"Zhou","sequence":"additional","affiliation":[{"name":"Lingang Laboratory","place":["Shanghai, China"]},{"id":[{"id":"https:\/\/ror.org\/030bhh786","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Life Science and Technology, ShanghaiTech University","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9945-6387","authenticated-orcid":true,"given":"Constance L","family":"Cepko","sequence":"additional","affiliation":[{"name":"Departments of Genetics and Ophthalmology, Blavatnik Institute, Harvard Medical School","place":["Boston, United States"]},{"id":[{"id":"https:\/\/ror.org\/006w34k90","id-type":"ROR","asserted-by":"publisher"}],"name":"Howard Hughes Medical Institute","place":["Boston, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"corresponding-author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"4374","published-online":{"date-parts":[[2024,5,10]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1007\/978-1-4614-0631-0_81","type":"journal-article","article-title":"Analysis of the RPE sheet in the rd10 retinal degeneration model","volume":"723","author":"Chrenek","year":"2012","journal-title":"Advances in Experimental Medicine and Biology"},{"key":"bib2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2023.105045","type":"journal-article","article-title":"An insulin-regulated arrestin domain protein controls hepatic glucagon action","volume":"299","author":"Dagdeviren","year":"2023","journal-title":"The Journal of Biological Chemistry"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1093\/hmg\/ddn323","type":"journal-article","article-title":"BEST1 expression in the retinal pigment epithelium is modulated by OTX family members","volume":"18","author":"Esumi","year":"2009","journal-title":"Human Molecular Genetics"},{"key":"bib4","doi-asserted-by":"publisher","DOI":"10.1101\/2021.10.04.463034","type":"preprint","article-title":"Protein complex prediction with alphafold-multimer","volume-title":"bioRxiv","author":"Evans","year":"2021"},{"key":"bib5","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/5829063","type":"journal-article","article-title":"Identification of redox and glucose-dependent Txnip Protein Interactions","volume":"2016","author":"Forred","year":"2016","journal-title":"Oxidative Medicine and Cellular Longevity"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"1795","DOI":"10.1016\/S0140-6736(06)69740-7","type":"journal-article","article-title":"Retinitis pigmentosa","volume":"368","author":"Hartong","year":"2006","journal-title":"Lancet"},{"key":"bib7","doi-asserted-by":"publisher","first-page":"770","DOI":"10.1016\/j.freeradbiomed.2017.04.018","type":"journal-article","article-title":"PARP inhibition protects mitochondria and reduces ROS production via PARP-1-ATF4-MKP-1-MAPK retrograde pathway","volume":"108","author":"Hocsak","year":"2017","journal-title":"Free Radical Biology & Medicine"},{"key":"bib8","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1146\/annurev-vision-100419-115156","type":"journal-article","article-title":"Retina metabolism and metabolism in the pigmented epithelium: a busy intersection","volume":"7","author":"Hurley","year":"2021","journal-title":"Annual Review of Vision Science"},{"key":"bib9","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms3958","type":"journal-article","article-title":"The structural basis for the negative regulation of thioredoxin by thioredoxin-interacting protein","volume":"5","author":"Hwang","year":"2014","journal-title":"Nature Communications"},{"key":"bib10","doi-asserted-by":"publisher","first-page":"4485","DOI":"10.1158\/0008-5472.CAN-04-2271","type":"journal-article","article-title":"Tumor suppressor VDUP1 increases p27(kip1) stability by inhibiting JAB1","volume":"65","author":"Jeon","year":"2005","journal-title":"Cancer Research"},{"key":"bib11","doi-asserted-by":"publisher","first-page":"874","DOI":"10.1002\/cne.22800","type":"journal-article","article-title":"Rearrangement of the cone mosaic in the retina of the rat model of retinitis pigmentosa","volume":"520","author":"Ji","year":"2012","journal-title":"The Journal of Comparative Neurology"},{"key":"bib12","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1167\/iovs.14-15398","type":"journal-article","article-title":"The effect of TIMP-1 on the cone mosaic in the retina of the rat model of retinitis pigmentosa","volume":"56","author":"Ji","year":"2014","journal-title":"Investigative Ophthalmology & Visual Science"},{"key":"bib13","doi-asserted-by":"publisher","DOI":"10.1186\/s12986-018-0242-6","type":"journal-article","article-title":"Hsp90\u03b2 knockdown in DIO mice reverses insulin resistance and improves glucose tolerance","volume":"15","author":"Jing","year":"2018","journal-title":"Nutrition & Metabolism"},{"key":"bib14","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","type":"journal-article","article-title":"Highly accurate protein structure prediction with AlphaFold","volume":"596","author":"Jumper","year":"2021","journal-title":"Nature"},{"key":"bib15","doi-asserted-by":"publisher","first-page":"11300","DOI":"10.1073\/pnas.0604056103","type":"journal-article","article-title":"Antioxidants reduce cone cell death in a model of retinitis pigmentosa","volume":"103","author":"Komeima","year":"2006","journal-title":"PNAS"},{"key":"bib16","doi-asserted-by":"publisher","first-page":"618","DOI":"10.1016\/j.cell.2010.03.039","type":"journal-article","article-title":"Characterizing light-regulated retinal microRNAs reveals rapid turnover as a common property of neuronal microRNAs","volume":"141","author":"Krol","year":"2010","journal-title":"Cell"},{"key":"bib17","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1038\/s41592-022-01488-1","type":"journal-article","article-title":"ColabFold: making protein folding accessible to all","volume":"19","author":"Mirdita","year":"2022","journal-title":"Nature Methods"},{"key":"bib18","doi-asserted-by":"publisher","first-page":"8357","DOI":"10.1073\/pnas.95.14.8357","type":"journal-article","article-title":"Normal retina releases a diffusible factor stimulating cone survival in the retinal degeneration mouse","volume":"95","author":"Mohand-Said","year":"1998","journal-title":"PNAS"},{"key":"bib19","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2023.104809","type":"journal-article","article-title":"HSP90\u03b1 is needed for the survival of rod photoreceptors and regulates the expression of rod PDE6 subunits","volume":"299","author":"Munezero","year":"2023","journal-title":"The Journal of Biological Chemistry"},{"key":"bib20","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22105381","type":"journal-article","article-title":"Retinal pigment epithelium remodeling in mouse models of retinitis pigmentosa","volume":"22","author":"Napoli","year":"2021","journal-title":"International Journal of Molecular Sciences"},{"key":"bib21","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1111\/joa.13667","type":"journal-article","article-title":"Structural abnormalities of retinal pigment epithelial cells in a light-inducible, rhodopsin mutant mouse","volume":"243","author":"Napoli","year":"2023","journal-title":"Journal of Anatomy"},{"key":"bib22","doi-asserted-by":"publisher","first-page":"37559","DOI":"10.1074\/jbc.M405473200","type":"journal-article","article-title":"Importin alpha1 (Rch1) mediates nuclear translocation of thioredoxin-binding protein-2\/vitamin D(3)-up-regulated protein 1","volume":"279","author":"Nishinaka","year":"2004","journal-title":"The Journal of Biological Chemistry"},{"key":"bib23","type":"software","article-title":"Colabfold","volume-title":"GitHub","author":"Ovchinnikov","year":"2021","unstructured":"Ovchinnikov S. 2021. Colabfold. GitHub. https:\/\/github.com\/sokrypton\/colabfold."},{"key":"bib24","doi-asserted-by":"publisher","first-page":"21884","DOI":"10.1074\/jbc.M600427200","type":"journal-article","article-title":"The interaction of thioredoxin with Txnip: evidence for formation of a mixed disulfide by disulfide exchange","volume":"281","author":"Patwari","year":"2006","journal-title":"The Journal of Biological Chemistry"},{"key":"bib25","doi-asserted-by":"publisher","first-page":"24996","DOI":"10.1074\/jbc.M109.018093","type":"journal-article","article-title":"Thioredoxin-independent regulation of metabolism by the alpha-arrestin proteins","volume":"284","author":"Patwari","year":"2009","journal-title":"The Journal of Biological Chemistry"},{"key":"bib26","doi-asserted-by":"publisher","first-page":"1359","DOI":"10.1242\/jcs.142539","type":"journal-article","article-title":"\u0391-arrestins - new players in Notch and GPCR signaling pathways in mammals","volume":"127","author":"Puca","year":"2014","journal-title":"Journal of Cell Science"},{"key":"bib27","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1038\/nn.2234","type":"journal-article","article-title":"Stimulation of the insulin\/mTOR pathway delays cone death in a mouse model of retinitis pigmentosa","volume":"12","author":"Punzo","year":"2009","journal-title":"Nature Neuroscience"},{"key":"bib28","doi-asserted-by":"publisher","DOI":"10.1101\/2023.10.09.561525","type":"preprint","article-title":"Cell Type-Focused Compound Screen in Human Organoids Reveals Molecules and Pathways Controlling Cone Photoreceptor Death","volume-title":"bioRxiv","author":"Spirig","year":"2023"},{"key":"bib29","doi-asserted-by":"publisher","first-page":"13161","DOI":"10.1093\/nar\/gku1089","type":"journal-article","article-title":"Opposing roles of mitochondrial and nuclear PARP1 in the regulation of mitochondrial and nuclear DNA integrity: implications for the regulation of mitochondrial function","volume":"42","author":"Szczesny","year":"2014","journal-title":"Nucleic Acids Research"},{"key":"bib30","doi-asserted-by":"publisher","first-page":"1446","DOI":"10.1172\/JCI79766","type":"journal-article","article-title":"Activated mTORC1 promotes long-term cone survival in retinitis pigmentosa mice","volume":"125","author":"Venkatesh","year":"2015","journal-title":"The Journal of Clinical Investigation"},{"key":"bib31","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1016\/0896-6273(92)90181-c","type":"journal-article","article-title":"A locus control region adjacent to the human red and green visual pigment genes","volume":"9","author":"Wang","year":"1992","journal-title":"Neuron"},{"key":"bib32","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1016\/j.omtm.2020.10.003","type":"journal-article","article-title":"In Situ detection of adeno-associated viral vector genomes with SABER-FISH","volume":"19","author":"Wang","year":"2020","journal-title":"Molecular Therapy. Methods & Clinical Development"},{"key":"bib33","doi-asserted-by":"publisher","first-page":"1167","DOI":"10.1016\/j.molcel.2013.01.035","type":"journal-article","article-title":"AMPK-dependent degradation of TXNIP upon energy stress leads to enhanced glucose uptake via GLUT1","volume":"49","author":"Wu","year":"2013","journal-title":"Molecular Cell"},{"key":"bib34","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.145029","type":"journal-article","article-title":"Nrf2 overexpression rescues the RPE in mouse models of retinitis pigmentosa","volume":"6","author":"Wu","year":"2021","journal-title":"JCI Insight"},{"key":"bib35","doi-asserted-by":"publisher","first-page":"1433","DOI":"10.1172\/JCI79735","type":"journal-article","article-title":"NRF2 promotes neuronal survival in neurodegeneration and acute nerve damage","volume":"125","author":"Xiong","year":"2015","journal-title":"The Journal of Clinical Investigation"},{"key":"bib36","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.66240","type":"journal-article","article-title":"AAV-Txnip prolongs cone survival and vision in mouse models of retinitis pigmentosa","volume":"10","author":"Xue","year":"2021","journal-title":"eLife"},{"key":"bib37","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a041289","type":"journal-article","article-title":"Gene therapies for retinitis pigmentosa that target glucose metabolism","volume":"01","author":"Xue","year":"2023","journal-title":"Cold Spring Harbor Perspectives in Medicine"},{"key":"bib38","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2217885120","type":"journal-article","article-title":"Chromophore supply modulates cone function and survival in retinitis pigmentosa mouse models","volume":"120","author":"Xue","year":"2023","journal-title":"PNAS"},{"key":"bib39","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1089\/hum.2015.130","type":"journal-article","article-title":"Cone-specific promoters for gene therapy of achromatopsia and other retinal diseases","volume":"27","author":"Ye","year":"2016","journal-title":"Human Gene Therapy"},{"key":"bib40","doi-asserted-by":"publisher","first-page":"1179","DOI":"10.15252\/emmm.201505298","type":"journal-article","article-title":"Microglial phagocytosis of living photoreceptors contributes to inherited retinal degeneration","volume":"7","author":"Zhao","year":"2015","journal-title":"EMBO Molecular Medicine"},{"key":"bib41","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1007\/s00441-012-1522-5","type":"journal-article","article-title":"Spatiotemporal pattern of rod degeneration in the S334ter-line-3 rat model of retinitis pigmentosa","volume":"351","author":"Zhu","year":"2013","journal-title":"Cell and Tissue Research"}],"container-title":["eLife"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdn.elifesciences.org\/articles\/90749\/elife-90749-v1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdn.elifesciences.org\/articles\/90749\/elife-90749-v1.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/elifesciences.org\/articles\/90749","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T10:29:46Z","timestamp":1787567386000},"score":1,"resource":{"primary":{"URL":"https:\/\/elifesciences.org\/articles\/90749"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,10]]},"references-count":41,"alternative-id":["10.7554\/eLife.90749"],"URL":"https:\/\/doi.org\/10.7554\/elife.90749","archive":["CLOCKSS"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2023.08.03.551766","asserted-by":"subject"},{"id-type":"doi","id":"10.1101\/2023.08.03.551766","asserted-by":"object"}],"is-same-as":[{"id-type":"doi","id":"10.7554\/eLife.90749.4","asserted-by":"subject"}],"is-version-of":[{"id-type":"doi","id":"10.7554\/eLife.90749.1","asserted-by":"subject"},{"id-type":"doi","id":"10.7554\/eLife.90749.2","asserted-by":"subject"},{"id-type":"doi","id":"10.7554\/eLife.90749.3","asserted-by":"subject"}]},"ISSN":["2050-084X"],"issn-type":[{"value":"2050-084X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,10]]},"assertion":[{"value":"single anonymised","name":"peer_review_transparency","label":"Peer review transparency","group":{"name":"peer_review_taxonomy"}},{"value":"other reviewer(s), editor","name":"peer_review_interaction","label":"Peer review interaction","group":{"name":"peer_review_taxonomy"}},{"value":"review summaries, review reports, author\/editor communication, reviewer identities reviewer opt in, editor identities","name":"peer_review_published","label":"Peer review published","group":{"name":"peer_review_taxonomy"}},{"value":"open (sign in with ORCID iD required)","name":"post_publication_commenting","label":"Post publication commenting","group":{"name":"post_publication_commenting"}}],"article-number":"RP90749"}}