Melanopsin Retinal Ganglion Cells Regulate Cone Photoreceptor Lamination in the Mouse Retina

Abstract

SUMMARY Newborn neurons follow molecular cues to reach their final destination, but whether early life experience influences lamination remains largely unexplored. As light is among the first stimuli to reach the developing nervous system via intrinsically photosensitive retinal ganglion cells (ipRGCs), we asked whether ipRGCs could affect lamination in the developing mouse retina. We show here that ablation of ipRGCs causes cone photoreceptors to mislocalize at different apicobasal positions in the retina. This effect is partly mediated by light-evoked activity in ipRGCs, as dark rearing or silencing of ipRGCs leads a subset of cones to mislocalize. Furthermore, ablation of ipRGCs alters the cone transcriptome and decreases expression of the dopamine receptor D4, while injection of L-DOPA or D4 receptor agonist rescues the displaced cone phenotype observed in dark-reared animals. These results show that early light-mediated activity in ipRGCs influences neuronal lamination and identify ipRGC-elicited dopamine release as a mechanism influencing cone position.

Gap Junction Coupling Shapes the Encoding of Light in the Developing Retina

“…Our functional analysis of ipRGC subtypes yielded several key findings. First, we identified multiple subtypes of ipRGCs and characterized their functional properties, consistent with previous studies that identified M1s [4,41], M2s [16], M4s [42], and other ON-stratifying ipRGCs [9] in neonatal mice. In contrast to our finding of six functional groups, an MEA study identified 3 functional groups [7].…”

Circadian regulation in the retina: From molecules to network

“…The intraretinal axon collaterals of ipRGCs project to dopaminergic amacrine cells and influence retinal light adaptation, as the deletion of M1 ipRGCs attenuates retinal light adaptation (Prigge et al., ). During development, ablation of ipRGCs causes mislocalization of a subset of cone photoreceptors in dark‐reared animals (Tufford et al., ).…”

Reprogramming of Adult Retinal Müller Glial Cells into Human-Induced Pluripotent Stem Cells as an Efficient Source of Retinal Cells

“…However, a progressive disorganization of the inner region of the structures was observed concurrently with the RGC loss that is expected in this type of cultures in the absence of central projection targets. The requirement of RGCs for proper retinal lamination has been demonstrated in mouse and zebrafish retina, where the developmental ablation of a RGC subpopulation or interfering with the RGC migration and positioning led to a lamination defect [49, 50]. Neuronal migration and lamination play a central role in the building of the retinal laminar architecture [51].…”