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Network","award":["77821"],"award-info":[{"award-number":["77821"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Background: Retinopathy of prematurity (ROP) is the major cause of blindness in children. It is a biphasic disease with retinal vessel growth cessation and loss (Phase I) followed by uncontrolled retinal vessel growth (Phase II). Folate is an essential nutrient for fetal development and growth. Premature infants have a high risk for folate deficiency. However, the contribution of folate to ROP risk remains unknown. Methods: In mouse oxygen-induced retinopathy (OIR), the nursing dams were fed with a folic acid-deficient or control diet after delivery until the end of hyperoxia. Alternatively, pups received direct injection of either folic acid or vehicle during Phase I hyperoxia. Genes involved in the folate cycle and angiogenic responses were examined using real-time PCR. Total retinal folate levels were measured with the Lactobacillus casei assay. Results: Maternal folic acid deficiency in early life exacerbated pathological retinal vessel growth, while supplementation with folic acid suppressed it. Genes involved in the folate cycle were downregulated in Phase I OIR retinas and were highly expressed in M\u00fcller glia. Folic acid reduced pro-angiogenic signaling in cultured rat retinal M\u00fcller glia in vitro. Conclusions: Appropriate supplementation of folic acid might be a new and safe treatment for ROP at an early stage.<\/jats:p>","DOI":"10.3390\/biom15020309","type":"journal-article","created":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T09:36:22Z","timestamp":1739957782000},"page":"309","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Folic Acid Supplementation Inhibits Proliferative Retinopathy of Prematurity"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9684-0340","authenticated-orcid":false,"given":"Shen","family":"Nian","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"},{"name":"Department of Pathology, Xi\u2019an Medical University, Xi\u2019an 710021, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3626-6801","authenticated-orcid":false,"given":"Yan","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katarina E.","family":"Heyden","sequence":"additional","affiliation":[{"name":"Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9664-3518","authenticated-orcid":false,"given":"Ga\u00ebl","family":"Cagnone","sequence":"additional","affiliation":[{"name":"Centre Hospitalier Universitaire Sainte-Justine Research Center, Montreal, QC H3T 1C5, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hitomi","family":"Yagi","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"},{"name":"Department of Ophthalmology, Keio University School of Medicine, Tokyo 160-8582, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8343-4426","authenticated-orcid":false,"given":"Myriam","family":"Boeck","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"},{"name":"Eye Center, Medical Center, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5992-9039","authenticated-orcid":false,"given":"Deokho","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5821-5477","authenticated-orcid":false,"given":"Victoria","family":"Hirst","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhanqing","family":"Hua","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeff","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1471-5360","authenticated-orcid":false,"given":"Chaomei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4996-9380","authenticated-orcid":false,"given":"Katherine","family":"Neilsen","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean-S\u00e9bastien","family":"Joyal","sequence":"additional","affiliation":[{"name":"Centre Hospitalier Universitaire Sainte-Justine Research Center, Montreal, QC H3T 1C5, Canada"},{"name":"Department of Pediatrics, Faculty of Medicine, Universit\u00e9 de Montr\u00e9al, Montreal, QC H3C 3J7, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martha S.","family":"Field","sequence":"additional","affiliation":[{"name":"Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8182-2983","authenticated-orcid":false,"given":"Zhongjie","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA 02115, 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