Comparative Analysis of Tyrosine Hydroxylase Amacrine Cells in the Mammalian Retina: Distribution and Quantification in Mouse, Rat, Ground Squirrel and Macaque Retinas

Abstract

Dopaminergic amacrine cells (DACs) are a subclass of amacrine cells that modulate retinal processing and light adaptation by releasing dopamine. Although the role of dopamine is largely conserved, their retinal distribution across mammals remains incompletely characterized. In mice, rats, thirteen-lined ground squirrels (TLGSs), and macaques, we systematically compared the localization, number, and topography of DACs by their expression of tyrosine hydroxylase (TH), a crucial enzyme in the biosynthesis of dopamine. In all species examined, TH+ cells were primarily located in the inner nuclear layer; however, there was a species-dependent influence on their number and distribution. Mice exhibited the highest density of TH+cells but completely lacked displaced TH+cells (dTH+cells) in the ganglion cell layer. Despite interspecies variation in the total number of TH+cells in the retina, the overall density in rats, TLGSs, and macaques was similar. Most species displayed a higher density of DACs toward central retinal regions. However, rats exhibited a distinctive dorsal concentration, particularly among dTH+cells. Although most species examined exhibited a similar ratio of TH+cells to Brn3a+ retinal ganglion cells, TLGSs showed a marked reduction, indicating a potentially diminished dopaminergic modulatory role. Species-specific DAC topographies aligned with specialized visual regions, such as the visual streak in TLGS and the macula in macaques. These results reveal both conserved and divergent features of retinal dopamine circuitry, reflecting evolutionary adaptations to visual processing demands.