{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T19:44:48Z","timestamp":1790192688025,"version":"4.1.0"},"reference-count":33,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2020,12,5]],"date-time":"2020-12-05T00:00:00Z","timestamp":1607126400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"KAKENHI","award":["16H03258"],"award-info":[{"award-number":["16H03258"]}]},{"name":"KAKENHI","award":["20K09834"],"award-info":[{"award-number":["20K09834"]}]},{"name":"KAKENHI","award":["18K09424"],"award-info":[{"award-number":["18K09424"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Recent studies have reported an association between myopia development and local ocular inflammation. Lactoferrin (LF) is an iron-binding protein present in saliva, tears, and mother\u2019s milk. Furthermore, sequestering iron by LF can cause its antibacterial property. Moreover, LF has an anti-inflammatory effect. We aimed to determine the suppressive effect of LF against the development and progress of myopia using a murine lens-induced myopia (LIM) model. We divided male C57BL\/6J mice (3 weeks old) into two groups. While the experimental group was orally administered LF (1600 mg\/kg\/day, from 3-weeks-old to 7-weeks-old), a similar volume of Ringer\u2019s solution was administered to the control group. We subjected the 4-week-old mice to \u221230 diopter lenses and no lenses on the right and left eyes, respectively. We measured the refraction and the axial length at baseline and 3 weeks after using a refractometer and a spectral domain optical coherence tomography (SD-OCT) system in both eyes. Furthermore, we determined the matrix metalloproteinase-2 (MMP-2) activity, and the amount of interleukin-6 (IL-6), MMP-2, and collagen 1A1 in the choroid or sclera. The eyes with a minus lens showed a refractive error shift and an axial length elongation in the control group, thus indicating the successful induction of myopia. However, there were no significant differences in the aforementioned parameters in the LF group. While LIM increased IL-6 expression and MMP-2 activity, it decreased collagen 1A1 content. However, orally administered LF reversed these effects. Thus, oral administration of LF suppressed lens-induced myopia development by modifying the extracellular matrix remodeling through the IL-6\u2013MMP-2 axis in mice.<\/jats:p>","DOI":"10.3390\/nu12123744","type":"journal-article","created":{"date-parts":[[2020,12,6]],"date-time":"2020-12-06T22:27:12Z","timestamp":1607293632000},"page":"3744","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Oral Bovine Milk Lactoferrin Administration Suppressed Myopia Development through Matrix Metalloproteinase 2 in a Mouse Model"],"prefix":"10.3390","volume":"12","author":[{"given":"Shin-Ichi","family":"Ikeda","sequence":"first","affiliation":[{"name":"Laboratory of Photobiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan"},{"name":"Department of Ophthalmology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, 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, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan"},{"name":"Department of Ophthalmology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6835-396X","authenticated-orcid":false,"given":"Masataro","family":"Toda","sequence":"additional","affiliation":[{"name":"Laboratory of Photobiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Jiang","sequence":"additional","affiliation":[{"name":"Laboratory of Photobiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan"},{"name":"Department of Ophthalmology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidemasa","family":"Torii","sequence":"additional","affiliation":[{"name":"Laboratory of Photobiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan"},{"name":"Department of Ophthalmology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, 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, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan"},{"name":"Tsubota Laboratory, Inc., 34 Shinanomachi, Shinjuku-ku, Tokyo 160-0016, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1038\/519276a","article-title":"The myopia boom","volume":"519","author":"Dolgin","year":"2015","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1016\/j.ophtha.2016.01.006","article-title":"Global prevalence of myopia and high myopia and temporal trends from 2000 through 2050","volume":"123","author":"Holden","year":"2016","journal-title":"Ophthalmology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1001\/jamaophthalmol.2016.4009","article-title":"Association of axial length with risk of uncorrectable visual impairment for Europeans with myopia","volume":"134","author":"Tideman","year":"2016","journal-title":"JAMA Ophthalmol."},{"key":"ref_4","first-page":"270","article-title":"Myopia and inflammation","volume":"6","author":"Herbort","year":"2011","journal-title":"J. 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