Evolution of neuronal cell classes and types in the vertebrate retina

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Summary

This large-scale comparative transcriptomic study across 17 vertebrate species reveals deep evolutionary conservation of retinal cell classes while showing increasing diversity toward the retinal output layer (RGCs), suggesting that species-specific visual adaptations occur primarily at the level of retinal output. The discovery that midget RGCs — which dominate the human retina and underpin high-acuity vision — have ancient evolutionary origins with mouse orthologues provides a new framework for using animal models to study human retinal diseases and visual processing.

Key Findings

Single-cell transcriptomic atlases were generated and integrated across 17 vertebrate species spanning humans, non-human primates, rodents, ungulates, opossum, ferret, tree shrew, bird, reptile, teleost fish, and lamprey.
Midget RGCs, which comprise >80% of RGCs in the human retina, were found to have rodent orthologues comprising only ~2% of mouse RGCs, with large receptive fields compared to the small fields of primate midget RGCs.
Evolutionary variation among cell types increases progressively from the outer retina (photoreceptors) to inner retina (RGCs), indicating that natural selection acts preferentially on retinal output circuits.
Both primate and mouse midget RGC orthologues show overrepresentation of projections to the thalamus (supplying primary visual cortex), supporting a shared ancestral function in cortical visual processing.
Major retinal subclasses are conserved across species, but cell-type-level variation is pronounced, with transcriptomic divergence correlating with evolutionary distance.