Age-related macular degeneration (AMD) is one of the leading causes of blindness in the elderly. Although genome-wide association studies have identified genetic variants associated with AMD, it has been challenging to identify the cell types driving this genetically complex disease. We performed single-cell RNA sequencing (scRNA-seq) of normal human retinas, and report the first single-cell human retinal transcriptomic atlas identifying all major cell types. Gene-expression heterogeneity was observed in Müller glial cells, suggesting that human retinal glia are more diverse than previously thought. The activity of genes associated with AMD was significantly enriched in vascular and glial cells, as well as in subpopulations of neurons. Furthermore, AMD disease-associated gene activity was consistent with regional macular disease susceptibility. Findings were validated using in situ hybridization techniques and immunofluorescence. Our data show how scRNA-seq can provide insight into relevant cell types for a complex genetic disease.
- Single-cell transcriptomic atlas of the human retina
- Identification of cell types associated with AMD
- Validation of findings using RNAscope
