Scholarlink

<p>G<sub>M1</sub>-gangliosidosis is a lysosomal storage disease characterized by the accumulation of G<sub>M1</sub> ganglioside in neurons, including retinal ganglion cells (RGCs). Although vision impairment and retinal degeneration are well-known manifestations in humans, knowledge about the underlying mechanism of these lesions is limited. Pathological retinal changes in a <i>Glb1</i> knockout (<i>Glb1</i><sup>−/−</sup>) mouse model were assessed using immunohistochemistry, immunofluorescence and transmission electron microscopy in 4- and 7-month-old wild type and <i>Glb1</i> knockout (<i>Glb1</i><sup>−/−</sup>) mice. Increased numbers of glial fibrillary acidic protein (GFAP) positive Müller cells (MCs) were detected in <i>Glb1</i><sup><i>−/−</i></sup> mice both at 4 and 7 months of age, indicating glial reactivity. A transient increase in glutamine synthetase (GS) positive MCs at 4 months of age with a subsequent decrease by 7 months, most likely related to reduced expression of GS, was also observed. Immunohistochemistry revealed loss of RGCs, storage material accumulation and decreased BRN3A expression in 7-month-old <i>Glb1</i><sup>−/−</sup> mice. Increasing numbers of Iba1-positive microglia/macrophages were detected in <i>Glb1</i><sup>−/−</sup> mice at both time points. Microglia/macrophages showed migration towards the inner retinal layers and acquired a morphological phenotype that indicates activation. The present study shows that the murine G<sub>M1</sub> model used in this study is suitable for investigating ocular changes in lysosomal storage diseases.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Novel insights into pathomechanisms of retinal neuronal degeneration and reactive gliosis in a murine model of GM1-gangliosidosis

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年8月13日

查看全文
  • Lorna Jubran,
  • Rouven Wannemacher,
  • Anastasiia Ulianytska,
  • Ingo Gerhauser,
  • Wolfgang Baumgärtner,
  • Eva Leitzen

摘要

GM1-gangliosidosis is a lysosomal storage disease characterized by the accumulation of GM1 ganglioside in neurons, including retinal ganglion cells (RGCs). Although vision impairment and retinal degeneration are well-known manifestations in humans, knowledge about the underlying mechanism of these lesions is limited. Pathological retinal changes in a Glb1 knockout (Glb1−/−) mouse model were assessed using immunohistochemistry, immunofluorescence and transmission electron microscopy in 4- and 7-month-old wild type and Glb1 knockout (Glb1−/−) mice. Increased numbers of glial fibrillary acidic protein (GFAP) positive Müller cells (MCs) were detected in Glb1−/− mice both at 4 and 7 months of age, indicating glial reactivity. A transient increase in glutamine synthetase (GS) positive MCs at 4 months of age with a subsequent decrease by 7 months, most likely related to reduced expression of GS, was also observed. Immunohistochemistry revealed loss of RGCs, storage material accumulation and decreased BRN3A expression in 7-month-old Glb1−/− mice. Increasing numbers of Iba1-positive microglia/macrophages were detected in Glb1−/− mice at both time points. Microglia/macrophages showed migration towards the inner retinal layers and acquired a morphological phenotype that indicates activation. The present study shows that the murine GM1 model used in this study is suitable for investigating ocular changes in lysosomal storage diseases.