{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T19:44:44Z","timestamp":1790192684576,"version":"4.1.0"},"reference-count":59,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2020,10,4]],"date-time":"2020-10-04T00:00:00Z","timestamp":1601769600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"KAKENHI","award":["18K09424"],"award-info":[{"award-number":["18K09424"]}]},{"name":"KAKENHI","award":["20K18393"],"award-info":[{"award-number":["20K18393"]}]},{"name":"KAKENHI","award":["17H06402"],"award-info":[{"award-number":["17H06402"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Neovascular retinal degeneration is a leading cause of blindness in advanced countries. Anti-vascular endothelial growth factor (VEGF) drugs have been used for neovascular retinal diseases; however, anti-VEGF drugs may cause the development of chorioretinal atrophy in chronic therapy as they affect the physiological amount of VEGF needed for retinal homeostasis. Hypoxia-inducible factor (HIF) is a transcription factor inducing VEGF expression under hypoxic and other stress conditions. Previously, we demonstrated that HIF was involved with pathological retinal angiogenesis in murine models of oxygen-induced retinopathy (OIR), and pharmacological HIF inhibition prevented retinal neovascularization by reducing an ectopic amount of VEGF. Along with this, we attempted to find novel effective HIF inhibitors. Compounds originally isolated from mushroom-forming fungi were screened for prospective HIF inhibitors utilizing cell lines of 3T3, ARPE-19 and 661W. A murine OIR model was used to examine the anti-angiogenic effects of the compounds. As a result, 2-azahypoxanthine (AHX) showed an inhibitory effect on HIF activation and suppressed Vegf mRNA upregulation under CoCl2-induced pseudo-hypoxic conditions. Oral administration of AHX significantly suppressed retinal neovascular tufts in the OIR model. These data suggest that AHX could be a promising anti-angiogenic agent in retinal neovascularization by inhibiting HIF activation.<\/jats:p>","DOI":"10.3390\/biom10101405","type":"journal-article","created":{"date-parts":[[2020,10,5]],"date-time":"2020-10-05T08:35:57Z","timestamp":1601886957000},"page":"1405","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["A Fairy Chemical Suppresses Retinal Angiogenesis as a HIF Inhibitor"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5992-9039","authenticated-orcid":false,"given":"Deokho","family":"Lee","sequence":"first","affiliation":[{"name":"Laboratory of Photobiology, Keio University School of Medicine, Tokyo 160-8582, Japan"},{"name":"Department of Ophthalmology, Keio University School of Medicine, Tokyo 160-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5377-6772","authenticated-orcid":false,"given":"Yukihiro","family":"Miwa","sequence":"additional","affiliation":[{"name":"Laboratory of Photobiology, Keio University School of Medicine, Tokyo 160-8582, Japan"},{"name":"Department of Ophthalmology, Keio University School of Medicine, Tokyo 160-8582, Japan"},{"name":"Animal Eye Care Tokyo Animal Eye Clinic, Tokyo 158-0093, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wu","sequence":"additional","affiliation":[{"name":"Research Institute of Green Science and Technology, Shizuoka University, Shizuoka 422-8529, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiho","family":"Shoda","sequence":"additional","affiliation":[{"name":"Laboratory of Photobiology, Keio University School of Medicine, Tokyo 160-8582, Japan"},{"name":"Department of Ophthalmology, Keio University School of Medicine, Tokyo 160-8582, Japan"},{"name":"Department of Ophthalmology, Nihon University School of Medicine, Tokyo 173-0032, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heonuk","family":"Jeong","sequence":"additional","affiliation":[{"name":"Laboratory of Photobiology, Keio University School of Medicine, Tokyo 160-8582, Japan"},{"name":"Department of Ophthalmology, Keio University School of Medicine, Tokyo 160-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirokazu","family":"Kawagishi","sequence":"additional","affiliation":[{"name":"Research Institute of Green Science and Technology, Shizuoka University, Shizuoka 422-8529, Japan"},{"name":"Graduate School of Integrated Science and Technology, Shizuoka University, Shizuoka 422-8529, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8874-7111","authenticated-orcid":false,"given":"Kazuo","family":"Tsubota","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Keio University School of Medicine, Tokyo 160-8582, Japan"},{"name":"Tsubota Laboratory, Inc., Tokyo 160-0016, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5457-2720","authenticated-orcid":false,"given":"Toshihide","family":"Kurihara","sequence":"additional","affiliation":[{"name":"Laboratory of Photobiology, Keio University School of Medicine, Tokyo 160-8582, Japan"},{"name":"Department of Ophthalmology, Keio University School of Medicine, Tokyo 160-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1007\/s11892-012-0283-6","article-title":"Current Epidemiology of Diabetic Retinopathy and Diabetic Macular Edema","volume":"12","author":"Ding","year":"2012","journal-title":"Curr. 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