中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2026, Vol. 21 ›› Issue (7): 3194-3201.doi: 10.4103/NRR.NRR-D-24-01270

• 原著:视神经损伤修复保护与再生 • 上一篇    下一篇

GPR88-Cre转基因小鼠具有天然恢复力但再生能力较差的视网膜神经节细胞类型鉴定

  

  • 出版日期:2026-07-15 发布日期:2026-03-31

Identification of a natively resilient but poorly regenerating retinal ganglion cell type in the G protein-coupled receptor 88-Cre transgenic mouse

Allison L. Hall1, †, Christopher Zhao1, Sean McCracken1, 2, Minglei Zhao1, Zelun Wang1, 2, 3, Andrea Santeford1, Rajendra S. Apte1, 4, 5, Philip R. Williams1, 6, 7, *   

  1. 1John F. Hardesty, MD Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO, USA; 
    2Graduate Program in Neuroscience, Washington University School of Medicine, St. Louis, MO, USA;  3Medical Scientist Training Program, Washington University School of Medicine, St. Louis, MO, USA;  4Department of Developmental Biology, Washington University in St. Louis School of Medicine, St. Louis, MO, USA; 5Department of Medicine, Washington University in St. Louis School of Medicine, St. Louis, MO, USA;  6Department of Neuroscience, Washington University School of Medicine, St. Louis, MO, USA;  7Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, USA
  • Online:2026-07-15 Published:2026-03-31
  • Contact: Philip R. Williams, PhD, prwillia@wustl.edu.
  • Supported by:
    This study was supported by an Institutional National Research Service Award T32 EY013360 (to SM and SW); Research to Prevent Blindness (Career Development Award; to PRW); BrightFocus Foundation (National Glaucoma Research; to PRW); Alcon Research Institute (Young Investigator Award; to PRW), and NIH Grants (EY032908, EY035684, EY036111; to PRW); the Jefferey T. Fort Innovation Fund and Siteman Retina Research Fund (to RSA); the Hope Center Viral Vectors Core at Washington University School of Medicine, an unrestricted grant (to the Department of Ophthalmology and Visual Sciences) from Research to Prevent Blindness; and Vision Core Grant (P30 EY002687).

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摘要：

视网膜神经节细胞易受神经退行性疾病影响，其死亡是导致常见不可逆视力丧失的主要原因。小鼠中存在46种转录特征独特的视网膜神经节细胞类型，它们对退行性变的易感性各不相同。近期转录组学实验定义了一种新型RGC细胞类型，该类型具有特别强的生存能力，并独特地高表达孤儿G蛋白偶联受体88。为研究这种视网膜神经节细胞类型，实验试图在GPR88-Cre转基因小鼠中识别新型存活能力强的视网膜神经节细胞并评估其存活与再生潜力。实验表明，这一未被识别的RGC类型很可能与先前描述的视神经方向选择性视网膜神经节细胞（ONdsRGCs）一致。有趣的是，实验发现ONdsRGC具有较强的抗损伤能力，但对已知再生治疗的响应能力有限。研究ONdsRGC的分子特性可能为保护患者视网膜神经节细胞开辟新的治疗途径。


https://orcid.org/0000-0003-4813-8925 (Philip R. Williams)

关键词: 轴突再生, G蛋白偶联受体, 神经保护, 视神经损伤, 视网膜

Abstract:

Retinal ganglion cells are susceptible to neurodegenerative conditions and their death drives common forms of irreversible vision loss. In mice, there are 46 transcriptionally unique retinal ganglion cell types that demonstrate different susceptibilities to degeneration. Recent transcriptional experiments defined a novel retinal ganglion cell type that survives particularly well and uniquely expresses high levels of the orphan G-protein-coupled receptor 88. Motivated to study this retinal ganglion cell type, we obtained GPR88-Cre transgenic mice to identify the novel well-surviving retinal ganglion cells and examine their survival and regenerative potential. Our experiments demonstrate that this unidentified retinal ganglion cell type is likely accordant with previously described ON-direction-selective retinal ganglion cells. Interestingly, we find that ON-direction-selective retinal ganglion cells are resilient, but demonstrate limited potential to regenerate their axons in response to well-characterized regenerative treatments. Studying the molecular properties of the ON-direction-selective retinal ganglion cells could unlock new therapeutics to preserve retinal ganglion cells in patients.

Key words: axon regeneration, G protein-coupled receptor, neuroprotection, optic nerve injury, retina, retinal ganglion cells