Developmental control of rod number via a light-dependent retrograde pathway from intrinsically photosensitive retinal ganglion cells

• Published in: Developmental cell Vol. 59; no. 21; pp. 2897 - 2911.e6
• Main Authors: D’Souza, Shane P., Upton, Brian A., Eldred, Kiara C., Glass, Ian, Nayak, Gowri, Grover, Kassidy, Ahmed, Abdulla, Nguyen, Minh-Thanh, Hu, Yueh-Chiang, Gamlin, Paul, Lang, Richard A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 04.11.2024
• Subjects: adaptation; ipRGCs; photoreceptor pruning; sensory experience; visual experience; visual experience; ipRGCs; sensory experience; adaptation; photoreceptor pruning
• ISSN: 1534-5807; 1878-1551; 1878-1551
• DOI: 10.1016/j.devcel.2024.07.018

Photoreception is essential for the development of the visual system, shaping vision’s first synapse to cortical development. Here, we find that the lighting environment controls developmental rod apoptosis via Opn4-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs). Using genetics, sensory environment manipulations, and computational approaches, we establish a pathway where light-dependent glutamate released from ipRGCs is detected via a transiently expressed glutamate receptor (Grik3) on rod precursors within the inner retina. Communication between these cells is mediated by hybrid neurites on ipRGCs that sense light before eye opening. These structures span the ipRGC-rod precursor distance over development and contain the machinery for photoreception (Opn4) and neurotransmitter release (Vglut2 & Syp). Assessment of the human gestational retina identifies conserved hallmarks of an ipRGC-to-rod axis, including displaced rod precursors, transient GRIK3 expression, and ipRGCs with deep-projecting neurites. This analysis defines an adaptive retrograde pathway linking the sensory environment to rod precursors via ipRGCs prior to eye opening. [Display omitted] •Light controls developing rod apoptosis through interactions with Opn4-expressing RGCs•ipRGCs project hybrid neurites into the developing inner retina, close to rods•Rods transiently express Grik3, allowing for signaling between ipRGCs and rods•Hallmarks of this retinal pathway are conserved between developing mice and humans Photoreception is crucial for the development of the visual system. D’Souza et al. identified a developmental light-dependent pathway that induces rod apoptosis through transient excitatory hybrid neurites on ipRGC photoreceptors, which appears conserved across mouse and human development.