Absence of Gut Microbiota Is Associated with RPE/Choroid Transcriptomic Changes Related to Age-Related Macular Degeneration Pathobiology and Decreased Choroidal Neovascularization

Int J Mol Sci. 2022 Aug 26;23(17):9676. doi: 10.3390/ijms23179676.

Abstract

Studies have begun to reveal significant connections between the gut microbiome and various retinal diseases, including age-related macular degeneration (AMD). 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-all 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-RPE/choroidal axis as well as a correlation with neovascular features of AMD.

Keywords: RNA sequencing; RPE–choroid; age-related macular degeneration; angiogenesis; choroidal neovascularization; germ-free mice; gut microbiome; gut–retina axis; microglia.

MeSH terms

  • Animals
  • Choroid / blood supply
  • Choroidal Neovascularization* / genetics
  • Choroidal Neovascularization* / pathology
  • Gastrointestinal Microbiome*
  • Macular Degeneration* / genetics
  • Macular Degeneration* / pathology
  • Mice
  • Mice, Inbred C57BL
  • Retinal Pigment Epithelium / pathology
  • Transcriptome