Development of cone photoreceptors and their synapses in the human and monkey fovea

• Published in: Journal of comparative neurology (1911) Vol. 527; no. 1; pp. 38 - 51
• Main Authors: Hendrickson, Anita, Zhang, Chi
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.01.2019
• Subjects: Animals; Bipolar cells; Calcium; Calcium channels (voltage-gated); Cones; Electron microscopy; Eye; Fetus; Fetuses; Fovea Centralis - embryology; Gestation; Glutamatergic transmission; Glutamic acid receptors (metabotropic); Humans; Immunocytochemistry; Macaca; Macaca fascicularis; Neurogenesis - physiology; Neurotransmission; Photoreceptors; Retina; Retinal Cone Photoreceptor Cells - cytology; RRID: AB_10000343; RRID: AB_10746416; RRID: AB_1860018; RRID: AB_2092368; RRID: AB_2253622; RRID: AB_2279325; RRID: AB_2314216; RRID: AB_2314780; RRID: AB_2314792; RRID: AB_2315298; RRID: AB_2315389/91; RRID: AB_2631101; RRID: AB_2631102; RRID: AB_399431; RRID: AB_477523; RRID: AB_887877; RRID: AB_94284; RRID: AB_94671; Synapses - ultrastructure; Synaptic ribbons; Synaptogenesis; RRID: AB_10746416; RRID: AB_94671; RRID: AB_887877; RRID: AB_2315389/91; RRID: AB_477523; RRID: AB_2314780; RRID: AB_2315298; RRID: AB_2314792; immunocytochemistry; RRID: AB_94284; RRID: AB_2314216; RRID: AB_10000343; RRID: AB_2253622; RRID: AB_2631101; RRID: AB_1860018; RRID: AB_2631102; retina; RRID: AB_2092368; electron microscopy; Macaca; RRID: AB_399431; RRID: AB_2279325
• ISSN: 0021-9967; 1096-9861
• DOI: 10.1002/cne.24170

During retinal development, ribbon synapse assembly in the photoreceptors is a crucial step involving numerous molecules. While the developmental sequence of plexiform layers in human retina has been characterized, the molecular steps of synaptogenesis remain largely unknown. In the present study, we focused on the central rod‐free region of primate retina, the fovea, to specifically investigate the development of cone photoreceptor ribbon synapses. Immunocytochemistry and electron microscopy were utilized to track the expression of photoreceptor transduction proteins and ribbon and synaptic markers in fetal human and Macaca retina. Although the inner plexiform layer appears earlier than the outer plexiform layer, synaptic proteins, and ribbons are first reliably recognized in cone pedicles. Markers first appear at fetal week 9. Both short (S) and medium/long (M/L) wavelength‐selective cones express synaptic markers in the same temporal sequence; this is independent of opsin expression which takes place in S cones a month before M/L cones. The majority of ribbon markers, presynaptic vesicular release and postsynaptic neurotransduction‐related machinery is present in both plexiform layers by fetal week 13. By contrast, two crucial components for cone to bipolar cell glutamatergic transmission, the metabotropic glutamate receptor 6 and voltage‐dependent calcium channel α1.4, are not detected until fetal week 22 when bipolar cell invagination is present in the cone pedicle. These results suggest an intrinsically programmed but nonsynchronous expression of molecules in cone synaptic development. Moreover, functional ribbon synapses and active neurotransmission at foveal cone pedicles are possibly present as early as mid‐gestation in human retina. Using immunocytochemistry and electron microscopy at various gestational time points in human and monkey retinas, this study suggests an intrinsically programmed, nonsynchronous expression of molecules in cone synaptic development. Ribbon synapses at foveal cone pedicles are present at midgestation in monkeys, and perhaps also in humans.