{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T18:17:32Z","timestamp":1790705852647,"version":"4.1.0"},"reference-count":44,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2022,12,2]],"date-time":"2022-12-02T00:00:00Z","timestamp":1669939200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Key generic technologies for third-party services based on health management","award":["CSTC, 2015shmh-ztzx10006"],"award-info":[{"award-number":["CSTC, 2015shmh-ztzx10006"]}]},{"name":"Key generic technologies for third-party services based on health management","award":["CSCT, 2020jscx-sbqwX0004"],"award-info":[{"award-number":["CSCT, 2020jscx-sbqwX0004"]}]},{"name":"Key generic technologies for third-party services based on health management","award":["CSTC, 2008CA5003"],"award-info":[{"award-number":["CSTC, 2008CA5003"]}]},{"name":"Chongqing High-tech Zone Application Study of Domestic in Vitro Diagnostic Medical Devices","award":["CSTC, 2015shmh-ztzx10006"],"award-info":[{"award-number":["CSTC, 2015shmh-ztzx10006"]}]},{"name":"Chongqing High-tech Zone Application Study of Domestic in Vitro Diagnostic Medical Devices","award":["CSCT, 2020jscx-sbqwX0004"],"award-info":[{"award-number":["CSCT, 2020jscx-sbqwX0004"]}]},{"name":"Chongqing High-tech Zone Application Study of Domestic in Vitro Diagnostic Medical Devices","award":["CSTC, 2008CA5003"],"award-info":[{"award-number":["CSTC, 2008CA5003"]}]},{"name":"Chongqing Key Laboratory of Ophthalmology","award":["CSTC, 2015shmh-ztzx10006"],"award-info":[{"award-number":["CSTC, 2015shmh-ztzx10006"]}]},{"name":"Chongqing Key Laboratory of Ophthalmology","award":["CSCT, 2020jscx-sbqwX0004"],"award-info":[{"award-number":["CSCT, 2020jscx-sbqwX0004"]}]},{"name":"Chongqing Key Laboratory of Ophthalmology","award":["CSTC, 2008CA5003"],"award-info":[{"award-number":["CSTC, 2008CA5003"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Purpose: To investigate the role of macrophage autophagy in the process of corneal neovascularization (CNV). Methods: In vivo, mice CNV was induced by alkali injury and compared with rapamycin-treated alkaline burn mice. Western blot was used to determine the autophagic status of the macrophages. We quantified the levels of macrophage polarization markers (CD86, INOS, CD163, CD206) by RT-qPCR and measured inflammatory factors through ELISA (IL-6 and TNF-\u03b1) in the early phase after injury. In vitro, the human umbilical vein endothelial cells (HUVECs) were co-cultured with macrophage-conditioned medium (MCM) induced by the THP-1 cell line to simulate the neovascular microenvironment. The vascularization capacity of HUVECs was examined using the CCK-8 assay kit, tube formation assay, and scratch wound-healing assay. Results: In vivo, the mRNA expression of Beclin-1 and ATG5 was increased, together with the upregulation of M1 macrophage markers (CD86 and INOS) in corneas after early alkali injury. The area of CNV is effectively relieved in the rapamycin-treated mice. In vitro, upregulation of autophagy level by pretreatment with 3-methyladenine (3-MA) could increase the mRNA expression of the M1 markers. Macrophage-conditioned medium with impaired autophagy contains more IL-6 and TNF-\u03b1 compared to the M1 macrophage-conditioned medium, promoting HUVEC proliferation, migration, and tube formation capacity. Enhancing the autophagy level with rapamycin (RAPA) could reverse this phenomenon. Conclusions: Impaired autophagy promoted macrophage polarization toward M1 type and increased the expression of IL-6 and TNF-\u03b1, which led to severe CNV. Using the autophagy activator (RAPA) could effectively alleviate CNV by promoting autophagy.<\/jats:p>","DOI":"10.3390\/cells11233895","type":"journal-article","created":{"date-parts":[[2022,12,2]],"date-time":"2022-12-02T03:00:36Z","timestamp":1669950036000},"page":"3895","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Impaired Autophagy Causes Severe Corneal Neovascularization"],"prefix":"10.3390","volume":"11","author":[{"given":"Kun","family":"Yi","sequence":"first","affiliation":[{"name":"Chongqing Key Laboratory of Ophthalmology and Chongqing Eye Institute, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuping","family":"Yang","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of Ophthalmology and Chongqing Eye Institute, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Yuan","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of Ophthalmology and Chongqing Eye Institute, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingqian","family":"Xiang","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of Ophthalmology and Chongqing Eye Institute, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanbi","family":"Zhou","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of Ophthalmology and Chongqing Eye Institute, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"108363","DOI":"10.1016\/j.exer.2020.108363","article-title":"Corneal neovascularization","volume":"202","author":"Nicholas","year":"2021","journal-title":"Exp. 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