Bulk and single-cell gene expression analyses reveal aging human choriocapillaris has pro-inflammatory phenotype

Microvasc Res. 2020 Sep:131:104031. doi: 10.1016/j.mvr.2020.104031. Epub 2020 Jun 9.

Abstract

The human choroidal vasculature is subject to age-related structural and gene expression changes implicated in age-related macular degeneration (AMD). In this study, we performed both bulk and single-cell RNA sequencing on infant (n = 4 for bulk experiments, n = 2 for single-cell experiments) and adult (n = 13 for bulk experiments, n = 6 for single-cell experiments) human donors to characterize how choroidal gene expression changes with age. Differential expression analysis revealed that aged choroidal samples were enriched in genes encoding pro-inflammatory transcription factors and leukocyte transendothelial cell migration adhesion proteins. Such genes were observed to be differentially expressed specifically within choroidal endothelial cells at the single-cell level. Immunohistochemistry experiments support transcriptional findings that CD34 is elevated in infant choriocapillaris endothelial cells while ICAM-1 is enriched in adults. These results suggest several potential drivers of the pro-inflammatory vascular phenotype observed with advancing age.

Keywords: Age-related macular degeneration; Choriocapillaris; Choroid; Infant; Pericytes; Single-cell.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Age Factors
  • Aged
  • Aged, 80 and over
  • Aging / genetics*
  • Aging / metabolism
  • Choroid / blood supply*
  • Endothelial Cells / metabolism*
  • Female
  • Gene Expression Regulation
  • Humans
  • Infant
  • Infant, Newborn
  • Inflammation / genetics*
  • Inflammation / metabolism
  • Inflammation Mediators / metabolism*
  • Macular Degeneration / genetics*
  • Macular Degeneration / metabolism
  • Male
  • Middle Aged
  • Phenotype
  • Sequence Analysis, RNA*
  • Single-Cell Analysis*

Substances

  • Inflammation Mediators