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As critical supporting tissues of the retina, the retinal pigment epithelium (RPE) and underlying choroid play a critical role in retinal homeostasis and degeneration. However, the relationship between the microbiome and RPE\/choroid remains poorly understood, particularly in animal models of AMD. In order to better elucidate this role, we performed high-throughput RNA sequencing of RPE\/choroid tissue in germ-free (GF) and specific pathogen-free (SPF) mice. Furthermore, utilizing a specialized laser-induced choroidal neovascularization (CNV) model that we developed, we compared CNV size and inflammatory response between GF and SPF mice. After correction of raw data, 660 differentially expressed genes (DEGs) were identified, including those involved in angiogenesis regulation, scavenger and cytokine receptor activity, and inflammatory response\u2014all of which have been implicated in AMD pathogenesis. Among lasered mice, the GF group showed significantly decreased CNV lesion size and microglial infiltration around CNV compared to the SPF group. Together, these findings provide evidence for a potential gut\u2013RPE\/choroidal axis as well as a correlation with neovascular features of AMD.<\/jats:p>","DOI":"10.3390\/ijms23179676","type":"journal-article","created":{"date-parts":[[2022,8,29]],"date-time":"2022-08-29T01:39:19Z","timestamp":1661737159000},"page":"9676","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Absence of Gut Microbiota Is Associated with RPE\/Choroid Transcriptomic Changes Related to Age-Related Macular Degeneration Pathobiology and Decreased Choroidal Neovascularization"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4632-7730","authenticated-orcid":false,"given":"Jason Y.","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Ophthalmology and Visual Science, University of Chicago, Chicago, IL 60637, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9246-9321","authenticated-orcid":false,"given":"Bingqing","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Chicago, Chicago, IL 60637, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hugo","family":"Barba","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Science, University of Chicago, Chicago, IL 60637, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Urooba","family":"Nadeem","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Chicago, Chicago, IL 60637, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Asadolah","family":"Movahedan","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Science, Yale University School of Medicine, New Haven, CT 06510, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nini","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Science, University of Chicago, Chicago, IL 60637, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melanie","family":"Spedale","sequence":"additional","affiliation":[{"name":"Animal Resources Center, University of Chicago, Chicago, IL 60637, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"D\u2019Souza","sequence":"additional","affiliation":[{"name":"Duchossois Family Institute, University of Chicago, Chicago, IL 60637, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wendy","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Science, University of Chicago, Chicago, IL 60637, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eugene B.","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Chicago, Chicago, IL 60637, USA"},{"name":"The Microbiome Center, University of Chicago, Chicago, IL 60637, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Betty","family":"Theriault","sequence":"additional","affiliation":[{"name":"Animal Resources Center, University of Chicago, Chicago, IL 60637, USA"},{"name":"Department of Surgery, University of Chicago, Chicago, IL 60637, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dinanath","family":"Sulakhe","sequence":"additional","affiliation":[{"name":"Duchossois Family Institute, University of Chicago, Chicago, IL 60637, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dimitra","family":"Skondra","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Science, University of Chicago, Chicago, IL 60637, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e106","DOI":"10.1016\/S2214-109X(13)70145-1","article-title":"Global Prevalence of Age-Related Macular Degeneration and Disease Burden Projection for 2020 and 2040: A Systematic Review and Meta-Analysis","volume":"2","author":"Wong","year":"2014","journal-title":"Lancet Glob. 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