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

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. [Display omitted] •Bulk or single-cell RNA sequencing were performed on 6 infant and 19 adult human donor choroids.•Differentially expressed genes were identified between infant and adult cells in all choroidal cell populations.•Distinct clusters of pericytes and vascular smooth muscle cells were characterized.•Aged human choroid demonstrated increased pro-inflammatory gene expression, particularly in endothelial cells.