Abstract
AbstractPhotoreception, a form of sensory experience, is essential for normal development of the mammalian visual system. Detecting photons during development is a prerequisite for visual system function - from vision’s first synapse at the cone pedicle and maturation of retinal vascular networks, to transcriptional establishment and maturation of cell types within the visual cortex. Consistent with this theme, we find that the lighting environment regulates developmental rod photoreceptor apoptosis via OPN4-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs). Using a combination of genetics, sensory environment manipulations, and computational approaches, we establish a molecular pathway in which light-dependent glutamate release from ipRGCs is detected via a transiently expressed kainate receptor (GRIK3) in immature rods localized to the inner retina. Communication between ipRGCs and nascent inner retinal rods appears to be mediated by unusual hybrid neurites projecting from ipRGCs that sense light before eye-opening. These structures, previously referred to as outer retinal dendrites (ORDs), span the ipRGC-immature rod distance over the first postnatal week and contain the machinery for sensory detection (melanopsin, OPN4) and axonal/anterograde neurotransmitter release (Synaptophysin, and VGLUT2). Histological and computational assessment of human mid-gestation development reveal conservation of several hallmarks of an ipRGC-to-immature rod pathway, including displaced immature rods, transientGRIK3expression in the rod lineage, and the presence of ipRGCs with putative neurites projecting deep into the developing retina. Thus, this analysis defines a retinal retrograde signaling pathway that links the sensory environment to immature rods via ipRGC photoreceptors, allowing the visual system to adapt to distinct lighting environments priory to eye-opening.
Publisher
Cold Spring Harbor Laboratory