{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T19:02:32Z","timestamp":1779908552633,"version":"3.53.1"},"reference-count":73,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"22","funder":[{"name":"General Research Fund (GRF) from the Hong Kong Research Grants Council","award":["15107823"],"award-info":[{"award-number":["15107823"]}]}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2026,5,29]]},"abstract":"<jats:p>\n                    Retinitis pigmentosa (RP), the most prevalent inherited retinal degeneration, features progressive photoreceptor loss with no approved disease-modifying therapies. While microglia-driven neuroinflammation accelerates RP progression, its sustaining mechanisms remain elusive. Through integrated multiomics profiling of retinal degeneration 10 (rd10) mice, we identify tropomyosin 1 (TPM1) as a previously unrecognized cytoskeletal-immune regulator orchestrating spatial neuroinflammation in RP. Genetic ablation of\n                    <jats:italic toggle=\"yes\">Tpm1<\/jats:italic>\n                    attenuated microglial reactivity and preserved vision, whereas overexpression triggered self-reinforcing inflammation via four interlocked axes: (i) TPM1-mediated activator protein-1 (AP-1) hyperactivation initiates senescence-associated secretory phenotype (SASP) through mitogen-activated protein kinase (MAPK) kinase\/extracellular signal\u2013regulated kinase 3\u2013dependent MAPK signaling; (ii) SASP subsequently mediates reduced phagocytosis; (iii)\n                    <jats:italic toggle=\"yes\">Tpm1-Apoe\/Fabp5<\/jats:italic>\n                    axis disruption precipitates lipid droplet accumulation with cholesterol crystallization; (iv) galectin-9 (LGALS9)\/CD45-mediated intermicroglial signaling propagates inflammatory signals across the retina. Our work redefines TPM1 as a linchpin in self-sustaining neurodegeneration cycles, where cytoskeletal dysfunction fuels immunometabolic collapse. These findings unveil precision therapeutic strategies targeting TPM1 hubs\u2014notably the LGALS9\/CD45 axis\u2014to disrupt inflammatory cycles while preserving retinal homeostasis.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aea6467","type":"journal-article","created":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T18:02:22Z","timestamp":1779904942000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["TPM1 drives cytoskeleton-immunometabolism coupling and LGALS9\/CD45-mediated neuroinflammatory propagation in retinitis pigmentosa"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1828-5713","authenticated-orcid":true,"given":"Rong","family":"Li","sequence":"first","affiliation":[{"name":"School of Optometry, The Hong Kong Polytechnic University, Hong Kong, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun-Qi","family":"Fan","sequence":"additional","affiliation":[{"name":"School of Optometry, The Hong Kong Polytechnic University, Hong Kong, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1309-3480","authenticated-orcid":true,"given":"Bin","family":"Lin","sequence":"additional","affiliation":[{"name":"School of Optometry, The Hong Kong Polytechnic University, Hong Kong, China."},{"name":"Research Centre for SHARP Vision (RCSV), The Hong Kong Polytechnic University, Hong Kong, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23094883"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12203"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms4517"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-024-04911-7"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01975"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-014-0186-3"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1059947"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20190009"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/1873-3468.14978"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5200-13.2014"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2016.06.004"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2013.10.011"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2012.12.001"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2013.09.009"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13566"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-022-02619-3"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/glia.24422"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2019.06.005"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/cne.21144"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adw9299"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-37304-3"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-21920-y"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40035-024-00402-3"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1007\/s001090050063"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cr.7290105"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07185-7"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2019.11.021"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20235939"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2016.09.001"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2013.11.018"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1210\/endocr\/bqab127"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M087890"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.adp8913"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19113515"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms16011806"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2016.09.053"},{"key":"e_1_3_2_38_2","first-page":"2965","article-title":"Tropomyosin \u2013 Master regulator of actin filament function in the cytoskeleton","volume":"128","author":"Gunning P. 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