Molecular specification of retinal cell types underlying central and peripheral vision in primates

Yi-Rong Peng, Karthik Shekhar, Wenjun Yan, Dustin Herrmann, Anna Sappington, Greg S. Bryman, Tavé van Zyl, Aviv Regev, Michael Tri. H. Do, Joshua R. Sanes

High acuity vision in primates, including humans, is mediated by a small central retinal region called the fovea. As more accessible model organisms lack a fovea, molecular underpinnings of its specialized function and its dysfunction in ocular diseases remain poorly understood. By analyzing >165,000 single-cell transcriptomes from macaque fovea and peripheral retina, we built cell taxonomies of >65 major cell types in each region. Most types correspond 1:1 between regions, but exhibit substantial differences in proportions and gene expression, some of which we relate to functional differences. Comparison of macaque and mouse retinal taxonomies demonstrate a tight correspondence across interneuron types. In contrast, projection neuron types, while expressing similar transcription factors, diverge in number, frequency distribution and expression. Key macaque retinal cell types and molecular features are conserved in humans, allowing elucidation of cell-type and region-specific expression patterns of >190 human retinal disease-associated genes.