Molecular analyses of the human retina and choroid at the single cell level

With few exceptions, every cell in the human body contains the exact same copy of DNA. However, each cell uses this DNA differently to express a unique subset of genes (in the form of RNA). Therefore, identifying which genes a cell expresses provides powerful insight into that cell’s function.

Historically, assaying gene expression in a heterogenous tissue required pooling RNA from all cells, making it challenging to pinpoint expression signatures from individual cell types. Advances in microfluidics and sequencing technology have addressed this major limitation, and gene expression can now be assayed at the level of individual cells. This technology, called single-cell RNA sequencing (scRNA-seq), has revolutionized our understanding of gene expression in heterogenous tissues.

We applied this new technology to study the molecular features of age-related macular degeneration (AMD), which is one of the most common cause of irreversible blindness globally. First, we generated an atlas of human retinal gene expression patterns at the single-cell level and compared gene expression across different retinal regions in health and disease. Second, we performed scRNA-seq on the human retinal pigment epithelium and choroid, two tissues that highly support vision physiology. We identified that choriocapillaris endothelial cells (which are the first cells to degenerate in AMD) exhibit several gene expression changes with advancing age (the greatest risk factor for AMD). Finally, we developed new bioinformatic tools to make scRNA-seq data more accessible to the vision research community.