{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:37:45Z","timestamp":1787027865757,"version":"build-2736575974"},"reference-count":102,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,8,18]],"date-time":"2021-08-18T00:00:00Z","timestamp":1629244800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK42086"],"award-info":[{"award-number":["DK42086"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Illinois Society for the Prevention of Blindness","award":["FP105447"],"award-info":[{"award-number":["FP105447"]}]},{"DOI":"10.13039\/100006312","name":"BrightFocus Foundation","doi-asserted-by":"publisher","award":["M2018042"],"award-info":[{"award-number":["M2018042"]}],"id":[{"id":"10.13039\/100006312","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The relationship between retinal disease, diet, and the gut microbiome has shown increasing importance over recent years. In particular, high-fat diets (HFDs) are associated with development and progression of several retinal diseases, including age-related macular degeneration (AMD) and diabetic retinopathy. However, the complex, overlapping interactions between diet, gut microbiome, and retinal homeostasis are poorly understood. Using high-throughput RNA-sequencing (RNA-seq) of whole retinas, we compare the retinal transcriptome from germ-free (GF) mice on a regular diet (ND) and HFD to investigate transcriptomic changes without influence of gut microbiome. After correction of raw data, 53 differentially expressed genes (DEGs) were identified, of which 19 were upregulated and 34 were downregulated in GF-HFD mice. Key genes involved in retinal inflammation, angiogenesis, and RPE function were identified. Enrichment analysis revealed that the top 3 biological processes affected were regulation of blood vessel diameter, inflammatory response, and negative regulation of endopeptidase. Molecular functions altered include endopeptidase inhibitor activity, protease binding, and cysteine-type endopeptidase inhibitor activity. Human and mouse pathway analysis revealed that the complement and coagulation cascades are significantly affected by HFD. This study demonstrates novel data that diet can directly modulate the retinal transcriptome independently of the gut microbiome.<\/jats:p>","DOI":"10.3390\/cells10082119","type":"journal-article","created":{"date-parts":[[2021,8,18]],"date-time":"2021-08-18T10:54:35Z","timestamp":1629284075000},"page":"2119","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["High-Fat Diet Alters the Retinal Transcriptome in the Absence of Gut Microbiota"],"prefix":"10.3390","volume":"10","author":[{"given":"David","family":"Dao","sequence":"first","affiliation":[{"name":"Department of Ophthalmology and Visual Science, University of Chicago, Chicago, IL 60637, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9246-9321","authenticated-orcid":false,"given":"Bingqing","family":"Xie","sequence":"additional","affiliation":[{"name":"Center for Research Informatics, University of Chicago, Chicago, IL 60637, USA"},{"name":"Department of Medicine, University of Chicago, Chicago, IL 60637, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Urooba","family":"Nadeem","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Chicago, Chicago, IL 60637, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Science, University of Chicago, Chicago, IL 60637, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asad","family":"Movahedan","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Science, Yale University School of Medicine, New Haven, CT 06437, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"D\u2019Souza","sequence":"additional","affiliation":[{"name":"Center for Research Informatics, University of Chicago, Chicago, IL 60637, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4012-4377","authenticated-orcid":false,"given":"Vanessa","family":"Leone","sequence":"additional","affiliation":[{"name":"Department of Animal Biologics and Metabolism, University of Wisconsin, Madison, WI 53706, USA"},{"name":"Knapp Center for Biomedical Discovery, Department of Medicine, Microbiome Medicine Program, University of Chicago, Chicago, IL 60637, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seenu M.","family":"Hariprasad","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Science, University of Chicago, Chicago, IL 60637, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugene B.","family":"Chang","sequence":"additional","affiliation":[{"name":"Knapp Center for Biomedical Discovery, Department of Medicine, Microbiome Medicine Program, University of Chicago, Chicago, IL 60637, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4680-1212","authenticated-orcid":false,"given":"Dinanath","family":"Sulakhe","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Chicago, Chicago, IL 60637, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitra","family":"Skondra","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Science, University of Chicago, Chicago, IL 60637, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1001\/jamaophthalmol.2015.5601","article-title":"Association of Dietary Nitrate Intake With Primary Open-Angle Glaucoma: A Prospective Analysis From the Nurses\u2019 Health Study and Health Professionals Follow-up Study","volume":"134","author":"Kang","year":"2016","journal-title":"JAMA Ophthalmol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1093\/ajcn\/79.5.755","article-title":"Dietary Fat Consumption and Primary Open-Angle Glaucoma","volume":"79","author":"Kang","year":"2004","journal-title":"Am. 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