Development of ON and OFF cholinergic amacrine cells in the human fetal retina.

Choline acetyltransferase (ChAT) expressing retinal amacrine cells are present across vertebrates. These interneurons play important roles in the development of retinal projections to the brain and in motion detection, specifically in generating direction‐selective responses to moving stimuli. ChAT amacrine cells typically comprise two spatially segregated populations that form circuits in the 'ON' or 'OFF' synaptic layers of the inner retina. This stereotypic arrangement is also found across the adult human retina, with the notable exception that ChAT expression is evident in the ON but not OFF layer of the fovea, a region specialized for high‐acuity vision. We thus investigated whether the human fovea exhibits a developmental path for ON and OFF ChAT cells that is retinal location‐specific. Our analysis shows that at each retinal location, human ON and OFF ChAT cells differentiate, form their separate synaptic layers, and establish non‐random mosaics at about the same time. However, unlike in the adult fovea, ChAT immunostaining is initially robust in both ON and OFF populations, up until at least mid‐gestation. ChAT expression in the OFF layer in the fovea is therefore significantly reduced after mid‐gestation. OFF ChAT cells in the human fovea and in the retinal periphery thus follow distinct maturational paths. Human cholinergic (ChAT) amacrine cells are first observed in the fovea at early‐gestation around fetal week (Fwk) 10, and become evident across the retina with age. Characteristic ON and OFF populations of ChAT cells with processes stratifying in separate bands in the synaptic neuropil emerge in the fovea by Fwk 11, and are present as late as mid‐gestation (Fwk 20). Previous work, however, demonstrate very few, if any, OFF ChAT‐immunoreactive cells in the adult human fovea (Rodieck & Marshak,). Thus, mechanisms must act to regulate ChAT expression differentially in the ON and OFF populations as the retina matures beyond mid‐gestation. [ABSTRACT FROM AUTHOR]