Oligodendrocyte Precursor Cells Shape Retinogeniculate Refinement Via a CHD8-Dependent Phagocytic Pathway

作者：Siyue Wen, Fen Guo, Zhidan Li, G. J. Huang, Minghe Shen, Xuelian He · 发表于：Investigative Ophthalmology & Visual Science · 年份：2026 · DOI：10.1167/iovs.67.3.64 · 研究领域：Retinal Development and Disorders、Neurogenesis and neuroplasticity mechanisms、Neuroscience and Neuropharmacology Research

Purpose: The most robust functional synaptic refinement in the dorsal lateral geniculate nucleus (dLGN) occurs around the time of eye opening. This study aimed to identify the major glial phagocyte responsible for eliminating excess synapses during this critical window, and to elucidate the molecular mechanisms underlying its regulation. Methods: Three-dimensional imaging was used to assess engulfment ability across glial subtypes, identifying the key population responsible for synaptic engulfment. In vivo ablation of these cells further confirmed their essential role in synaptic pruning. Differential transcriptomic analysis then revealed the core transcriptional regulator driving phagocytosis-related gene expression in this glial population. Conditional knockout mice combined with in vivo electrophysiological assessment of visual function were used to illustrate how this regulator shapes synaptic development by controlling phagocytic glial function. Results: Our findings revealed that oligodendrocyte precursor cells (OPCs) act as the major cells responsible for synaptic phagocytosis during this stage, and their ablation leads to excessive excitatory synapses in the dLGN. Single-cell sequencing analysis identified a distinct OPC subpopulation exhibiting high phagocytic gene expression independent of myelination. This subpopulation is enriched for the high-risk autism-associated gene Chd8. Genomic occupancy analysis showed that CHD8 directly promotes phagocytosis-related gene ...