Scholarlink

<p>The integrity of the blood-retinal barrier remains largely unexplored in glaucoma. Here we show that elevated intraocular pressure partially compromises the blood-retinal barrier in three distinct mouse models of glaucoma. This compromise induces subtle leakage without bleeding or detectable disruption of endothelial cell junctions and precedes neurodegeneration. Leakage occurs from peripheral veins in the retinal ganglion cell layer with a concomitant loss of the transcytosis inhibitor MFSD2A. RNA-sequencing, protein analyses and electron microscopy support enhanced transcytosis as the mechanism for leakage, although a subtle and partial junctional component cannot be ruled out. Importantly, stabilizing β-catenin in retinal endothelial cells prevents both vascular leakage and neurodegeneration. We further detect ganglion cell layer-specific leakage in 14/17 human primary open-angle glaucoma eyes but not in age-matched controls. The high incidence of leakage in mouse models and the human glaucoma eyes suggests that blood-retinal barrier compromise may be a common mechanism of glaucoma.</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

Intraocular pressure induced blood retinal barrier compromise in mouse models and human glaucoma

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月8日

查看全文
  • Chi Zhang,
  • Haeyn Lim,
  • Jennifer D. Ballheim,
  • Marina Simón,
  • Rui Fu,
  • Nicholas G. Tolman,
  • Logan J. Horbal,
  • Felicia A. Juarez,
  • Qing Wang,
  • Aakriti Bhandari,
  • Christa Montgomery,
  • Ling Zhu,
  • Jonathan G. Crowston,
  • Nicolas Robine,
  • Michael P. Fautsch,
  • Michael H. Elliott,
  • Simon W. M. John

摘要

The integrity of the blood-retinal barrier remains largely unexplored in glaucoma. Here we show that elevated intraocular pressure partially compromises the blood-retinal barrier in three distinct mouse models of glaucoma. This compromise induces subtle leakage without bleeding or detectable disruption of endothelial cell junctions and precedes neurodegeneration. Leakage occurs from peripheral veins in the retinal ganglion cell layer with a concomitant loss of the transcytosis inhibitor MFSD2A. RNA-sequencing, protein analyses and electron microscopy support enhanced transcytosis as the mechanism for leakage, although a subtle and partial junctional component cannot be ruled out. Importantly, stabilizing β-catenin in retinal endothelial cells prevents both vascular leakage and neurodegeneration. We further detect ganglion cell layer-specific leakage in 14/17 human primary open-angle glaucoma eyes but not in age-matched controls. The high incidence of leakage in mouse models and the human glaucoma eyes suggests that blood-retinal barrier compromise may be a common mechanism of glaucoma.