{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T01:01:26Z","timestamp":1779930086332,"version":"3.53.1"},"reference-count":53,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,2,20]],"date-time":"2025-02-20T00:00:00Z","timestamp":1740009600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Intraocularly, fatty acid-binding protein 4 (FABP4) and 5 (FABP5) mainly originate from human ocular choroidal fibroblasts (HOCF), and human nonpigmented ciliary epithelium (HNPCE) cells have been suggested to be pivotally involved in intraocular pathophysiology. To elucidate the unidentified regulatory mechanisms of the gene expression and protein secretion of FABPs, the effects of glucose levels, fatty acids (FAs), and peroxisome proliferator-activated receptor (PPAR) modulators were studied. To elucidate the additional biological role of FABPs, laser choroidal neovascularization (CNV) in Fabp4\u2212\/\u2212 and Fabp4\/5\u2212\/\u2212 mice was analyzed by fluorescein angiography. By changing glucose levels, the secretion and expression of FABP4 in HOCF were significantly upregulated, whereas the secretion and expression of FABP5 in HNPCE decreased. The administration of various FAs, particularly docosahexaenoic acid (DHA), markedly increased the expression and secretion of both FABPs. PPAR modulators also influenced the secretion and expression of FABPs. In vivo, wild-type retina exhibited evident CNV with high fluorescein intensity, while Fabp4\u2212\/\u2212 retina showed reduced CNV formation and Fabp4\/5\u2212\/\u2212 retina displayed evident CNV along with vitreous leakage. These findings suggest that (1) the production and secretion of intraocular FABP4 and FABP5 are distinctly regulated by glucose levels, FAs, and PPARs; and (2) intraocular FABP4 and FABP5 are critical for inducing retinal neovascularization and maintaining the blood-aqueous barrier.<\/jats:p>","DOI":"10.3390\/ijms26051791","type":"journal-article","created":{"date-parts":[[2025,2,20]],"date-time":"2025-02-20T04:03:17Z","timestamp":1740024197000},"page":"1791","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Expression and Secretion of Intraocular Fatty Acid-Binding Protein 4 (ioFABP4) and 5 (ioFABP5) Are Regulated by Glucose Levels and Fatty Acids"],"prefix":"10.3390","volume":"26","author":[{"given":"Hiroshi","family":"Ohguro","sequence":"first","affiliation":[{"name":"Departments of Ophthalmology, Sapporo Medical University, S1W17, Chuo-ku, Sapporo 060-8556, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0534-0257","authenticated-orcid":false,"given":"Megumi","family":"Higashide","sequence":"additional","affiliation":[{"name":"Departments of Ophthalmology, Sapporo Medical University, S1W17, Chuo-ku, Sapporo 060-8556, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika","family":"Ishiwata","sequence":"additional","affiliation":[{"name":"Departments of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University, S1W17, Chuo-ku, Sapporo 060-8556, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0124-5494","authenticated-orcid":false,"given":"Fumihito","family":"Hikage","sequence":"additional","affiliation":[{"name":"Departments of Ophthalmology, Sapporo Medical University, S1W17, Chuo-ku, Sapporo 060-8556, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8026-6532","authenticated-orcid":false,"given":"Megumi","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Departments of Ophthalmology, Sapporo Medical University, S1W17, Chuo-ku, Sapporo 060-8556, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9894-8523","authenticated-orcid":false,"given":"Nami","family":"Nishikiori","sequence":"additional","affiliation":[{"name":"Departments of Ophthalmology, Sapporo Medical University, S1W17, Chuo-ku, Sapporo 060-8556, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7876-1772","authenticated-orcid":false,"given":"Tatsuya","family":"Sato","sequence":"additional","affiliation":[{"name":"Departments of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University, S1W17, Chuo-ku, Sapporo 060-8556, Japan"},{"name":"Departments of Cellular Physiology and Signal Transduction, Sapporo Medical University, S1W17, Chuo-ku, Sapporo 060-8556, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0145-3541","authenticated-orcid":false,"given":"Masato","family":"Furuhashi","sequence":"additional","affiliation":[{"name":"Departments of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University, S1W17, Chuo-ku, Sapporo 060-8556, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.gene.2018.07.035","article-title":"Diverse roles of fatty acid binding proteins (FABPs) in development and pathogenesis of cancers","volume":"676","author":"Amiri","year":"2018","journal-title":"Gene"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1373\/clinchem.2005.062463","article-title":"Adipocyte fatty acid-binding protein is a plasma biomarker closely associated with obesity and metabolic syndrome","volume":"52","author":"Xu","year":"2006","journal-title":"Clin. 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