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

Shane P. D'Souza, Division of Pediatric Ophthalmology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Science of Light Center, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Abrahamson Pediatric Eye Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA. Electronic address: shane.dsouza@cchmc.org.
Brian A. Upton, Division of Pediatric Ophthalmology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Science of Light Center, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Abrahamson Pediatric Eye Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Kiara C. Eldred, Department of Biological Structure, University of Washington, Seattle, WA 98195, USA.
Ian Glass, Birth Defects Research Laboratory, Institute for Stem Cell and Regenerative Medicine, University of Washington School of Medicine, Seattle, WA 98109, USA; Department of Pediatrics, University of Washington, Seattle, WA 98195, USA; Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA 98195, USA.
Gowri Nayak, Transgenic Animal and Genome Editing Core, Department of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Kassidy Grover, Division of Hematology and Oncology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Neuroscience Graduate Program, University of Cincinnati, Cincinnati, OH 45229, USA.
Abdulla Ahmed, Medical Doctor (M.D.) Training Program, George Washington University School of Medicine, Washington, DC 20052, USA.
Minh-Thanh Nguyen, Division of Pediatric Ophthalmology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Science of Light Center, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Abrahamson Pediatric Eye Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Yueh-Chiang Hu, Transgenic Animal and Genome Editing Core, Department of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Paul Gamlin, Department of Ophthalmology and Visual Sciences, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Richard A. Lang, Division of Pediatric Ophthalmology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Science of Light Center, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Abrahamson Pediatric Eye Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Department of Ophthalmology, University of Cincinnati, Cincinnati, OH 45229, USA. Electronic address: richard.lang@cchmc.org.

Document Type

Journal Article

Publication Date

8-8-2024

Journal

Developmental cell

DOI

10.1016/j.devcel.2024.07.018

Keywords

adaptation; ipRGCs; photoreceptor pruning; sensory experience; visual experience

Abstract

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.

Department

School of Medicine and Health Sciences Student Works

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