June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
RNA Sequencing Reveals Changes in Mouse Retinal Transcriptome Caused by High-Fat Diet Induced Gut Dysbiosis
Author Affiliations & Notes
  • Urooba Nadeem
    Pathology, University of Chicago Division of the Biological Sciences, Chicago, Illinois, United States
  • Bingqing Xie
    Center of Research Informatics, University of Chicago Division of the Biological Sciences, Chicago, Illinois, United States
  • Mark D Souza
    Center of Research Informatics, University of Chicago Division of the Biological Sciences, Chicago, Illinois, United States
  • Asad Movehedan
    Yale University School of Medicine, New Haven, Connecticut, United States
  • Hugo Barba
    Ophthalmology, University of Chicago Division of the Biological Sciences, Chicago, Illinois, United States
  • Edward Xie
    Rosalind Franklin University of Medicine and Science Chicago Medical School, North Chicago, Illinois, United States
  • David Dao
    Ophthalmology, University of Chicago Division of the Biological Sciences, Chicago, Illinois, United States
  • Eugene Chang
    Department of Medicine, Microbiome Medicine Program, Knapp Center for Biomedical Discovery, University of Chicago Division of the Biological Sciences, Chicago, Illinois, United States
  • Dinnath sulakhe
    Center of Research Informatics, University of Chicago Division of the Biological Sciences, Chicago, Illinois, United States
  • Dimitra Skondra
    Ophthalmology, University of Chicago Division of the Biological Sciences, Chicago, Illinois, United States
  • Footnotes
    Commercial Relationships   Urooba Nadeem, None; Bingqing Xie, None; Mark Souza, None; Asad Movehedan, None; Hugo Barba, None; Edward Xie, None; David Dao, None; Eugene Chang, None; Dinnath sulakhe, None; Dimitra Skondra, None
  • Footnotes
    Support  1. 1. Bright Focus- Role of Diet and Gut Microbes in Macular Degeneration- M2018042- Dimitra Skondra 2. Women’s board University of Chicago, Dimitra Skondra 3. Illinois Society for Prevention of Blindness- Dimitra Skondra and Asadollah Movehedan 4. NIDDK P30 DK42086 for germ-free mice- Dr. Eugene Chang
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 2236. doi:
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      Urooba Nadeem, Bingqing Xie, Mark D Souza, Asad Movehedan, Hugo Barba, Edward Xie, David Dao, Eugene Chang, Dinnath sulakhe, Dimitra Skondra; RNA Sequencing Reveals Changes in Mouse Retinal Transcriptome Caused by High-Fat Diet Induced Gut Dysbiosis. Invest. Ophthalmol. Vis. Sci. 2021;62(8):2236.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : High-fat diet (HFD) alters the composition of the gut-microbiome-a condition known as gut dysbiosis. Both HFD and gut microbiome are implicated in the pathogenesis of retinal diseases including age-related macular degeneration (AMD) and diabetic retinopathy (DR). However, retinal transcriptome changes secondary to diet-induced gut dysbiosis have not been delineated. Here, we study the effect of HFD-induced gut dysbiosis on retinal gene expression and biologic pathways.

Methods : Fifteen weeks-old male C57BL/6J wild-type mice on normal diet (ND) and 23% HFD for 8 weeks were used (4 mice/group). Bacterial community structure is assessed from fecal DNA using 16S rRNA sequencing done on the Illumina MiSeq DNA platform and analyzed via QIIME software to determine the relative microbiome abundance. Whole retina RNA-sequencing (RNA-seq) was performed on NovaSEQ6000 using the paired-end method. Differentially expressed genes (DEGs) were identified (p-value <0.01); biologic pathways associated with the DEGs were found using the Kyoto Encyclopedia of Genes and Genomes (KEGG). Functional enrichment network and upstream transcription factor analysis were performed using EnrichR.

Results : Mice fed HFD have increased relative abundance of phyla of Firmicutes and Verrucomicrobia and decreased abundance of Bacteroides phylum. RNA seq identified a cohort of 30 DEGs, 14 of which were upregulated, and 16 were downregulated in the HFD group. DEGs included hypermethylated in cancer 1 (HIC1) and heat shock protein family A member 1B (Hspa1b) which are strongly associated with AMD. Pathway analysis revealed that DEGs are involved in purine, pyrimidine, arginine, and glutathione metabolism and mitogen-activated protein kinases (MAPK), cGMP-dependent protein kinase (cGMP-PKG), and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathways. Transcription factor polymerase 1(PARP1) and forkhead fox M1 (FOXM1) involved in retinal degeneration and epithelial-mesenchymal transformation of retinal pigment epithelium cells, respectively were also affected.

Conclusions : To our knowledge, this is the first study demonstrating that HFD-induced gut-dysbiosis regulates the retinal transcriptome, involving genes known to play a key role in AMD. Altering the gut microbiome via diet may have future implications for treating retinal diseases, especially AMD.

This is a 2021 ARVO Annual Meeting abstract.

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