High-fat diet alters the retinal transcriptome in the absence of gut microbiota

David Dao, Bingqing Xie, Urooba Nadeem, Jason Xiao, Asad Movahedan, Mark D’souza, Vanessa Leone, Seenu M. Hariprasad, Eugene B. Chang, Dinanath Sulakhe, Dimitra Skondra

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number2119
JournalCells
Volume10
Issue number8
DOIs
StatePublished - Aug 2021
Externally publishedYes

Keywords

  • Age-related macular degeneration
  • Angiogenesis
  • Complement cascade
  • Germ-free mice
  • Gut microbiome
  • Gut-retina axis
  • High-fat diet
  • Retinal inflammation
  • RNA sequencing

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint

Dive into the research topics of 'High-fat diet alters the retinal transcriptome in the absence of gut microbiota'. Together they form a unique fingerprint.

Cite this