{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T20:49:38Z","timestamp":1790628578826,"version":"4.1.0"},"reference-count":45,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"20","funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["no.82225013"],"award-info":[{"award-number":["no.82225013"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["no.81970809"],"award-info":[{"award-number":["no.81970809"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82271107"],"award-info":[{"award-number":["82271107"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["YG2025ZD04"],"award-info":[{"award-number":["YG2025ZD04"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shanghai Municipal Health Commission Collaborative Innovation Cluster Project","award":["2024CXJQ02"],"award-info":[{"award-number":["2024CXJQ02"]}]}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2026,5,15]]},"abstract":"<jats:p>\n                    Pericyte loss is an early and critical event in the pathogenesis of diabetic retinopathy (DR), yet the molecular mechanisms underlying pericyte dysfunction remain incompletely understood. Using single-cell RNA sequencing, we generated a retinal cellular overview comprising 37,982 cells from diabetic and nondiabetic mice. We identified a previously unrecognized pericyte subpopulation defined by high expression of pituitary tumor\u2013transforming gene 1 (\n                    <jats:italic toggle=\"yes\">Pttg1<\/jats:italic>\n                    ), which was enriched in diabetic retina. Functional studies demonstrated that CRISPR-Cas9\u2013 or small interfering RNA\u2013mediated silencing of\n                    <jats:italic toggle=\"yes\">PTTG1<\/jats:italic>\n                    restored pericyte stability and barrier-supporting function under high-glucose stress. In vivo,\n                    <jats:italic toggle=\"yes\">Pttg1<\/jats:italic>\n                    silencing via viral or pericyte-specific adeno-associated virus delivery improved retinal vascular integrity and reduced retinal vascular dysfunction in diabetic mice. Integrated transcriptomic and metabolomic profiling revealed that\n                    <jats:italic toggle=\"yes\">PTTG1<\/jats:italic>\n                    silencing reprogrammed metabolism, modulating glycolytic flux and attenuating oxidative stress. Furthermore, a therapeutic strategy using spherical nucleic acid\u2013based si\n                    <jats:italic toggle=\"yes\">Pttg1<\/jats:italic>\n                    nanocarriers (sTDN-si\n                    <jats:italic toggle=\"yes\">Pttg1<\/jats:italic>\n                    ) substantially ameliorated retinal vascular dysfunction in DR model. These findings suggest that PTTG1 is a critical regulator of pericyte metabolic homeostasis and microvascular function in DR, highlighting its translational potential as a therapeutic target for diabetic microvascular complications.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aea0542","type":"journal-article","created":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T17:59:07Z","timestamp":1778867947000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":1,"title":["Functional targeting of PTTG1 in pericytes restores vascular integrity in diabetic retina"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-7020-8355","authenticated-orcid":true,"given":"Linyu","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China."},{"name":"Affiliated Eye Hospital, Nanjing Medical University, Nanjing 210000, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China."},{"name":"Eye Institute and Department of Ophthalmology, Eye &amp; ENT Hospital, Fudan University, Shanghai 200030, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyue","family":"Zhang","sequence":"additional","affiliation":[{"name":"Affiliated Eye Hospital, Nanjing Medical University, Nanjing 210000, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Xia","sequence":"additional","affiliation":[{"name":"Affiliated Eye Hospital, Nanjing Medical University, Nanjing 210000, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaosa","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mudi","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanfei","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China."},{"name":"Affiliated Eye Hospital, Nanjing Medical University, Nanjing 210000, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China."},{"name":"Affiliated Eye Hospital, Nanjing Medical University, Nanjing 210000, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan","family":"Mu","sequence":"additional","affiliation":[{"name":"Eye Institute and Department of Ophthalmology, Eye &amp; ENT Hospital, Fudan University, Shanghai 200030, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiao","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0390-5440","authenticated-orcid":true,"given":"Jin","family":"Yao","sequence":"additional","affiliation":[{"name":"Affiliated Eye Hospital, Nanjing Medical University, Nanjing 210000, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7338-6413","authenticated-orcid":true,"given":"Biao","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","first-page":"CD013775","article-title":"Prognostic factors for the development and progression of proliferative diabetic retinopathy in people with diabetic retinopathy","volume":"2","author":"Perais J.","year":"2023","unstructured":"J. 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