Transplantation of human stem cell-derived neurons for retinal ganglion cell replacement and optic nerve regeneration.

移植人类干细胞衍生的神经元,用于视网膜神经节细胞替代和视神经再生。

基本信息

  • 批准号:
    10039636
  • 负责人:
  • 金额:
    $ 18.84万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-09-30 至 2025-08-31
  • 项目状态:
    未结题

项目摘要

Project Summary / Abstract Optic neuropathy causes irreversible vision loss because humans and other mammals cannot repair the optic nerve or repopulate the nerve cells that comprise it (retinal ganglion cells or RGCs). Glaucoma, the most common optic neuropathy, is projected to affect more than 110 million people by 2040, and to cause bilateral blindness in more than 10% of them. Stem cell therapy holds great potential for treating neurodegenerative diseases that currently have no cure, including glaucoma and other optic neuropathies. By generating human RGCs in a dish and transplanting them into the eye, it might be possible to replace lost RGCs, regenerate the optic nerve, and reverse blindness from optic neuropathy. Achieving RGC replacement will require significant advances in our ability to ensure survival of transplanted cells and facilitate their communication (integration) with the visual system. Significant work is ongoing to develop methods to drive RGC nerve fiber (axon) growth towards visual centers in the brain. However, RGC survival after transplantation and communication with other neurons in the retina (i.e. bipolar and amacrine cells) are equally important and have been less well studied. Through this mentored clinician-scientist career development project, Dr. Thomas Johnson proposes to advance the field of stem cell transplantation for optic nerve regeneration by improving survival and retinal integration of transplanted human RGCs. To so, he will address three specific aims: (1) Generation of novel human cell lines genetically engineered for improved survival after transplantation by targeting molecular pathways involved in RGC death and neuroprotection; (2) Determination of how optic nerve neurodegenerative disease states affect survival and integration of RGCs transplanted into the eye; and (3) Elucidation of how transplanted RGCs sense barriers to retinal integration and development of methods for overcoming these obstacles. The proposed work will address key limitations of prior translational optic nerve regeneration research by using experimental models that are more applicable to human disease, increasing the experimental rigor of transplant outcome assessments, determining which RGC subtypes are most likely to survive and integrate, and controlling for “material transfer” from transplanted cells to the recipient retina. Dr. Johnson is an early-career glaucoma specialist and neuroscientist who will conduct this project in an outstanding research environment at Johns Hopkins’ Wilmer Eye Institute, under the mentorship of an interdisciplinary team of senior investigators, including Drs. Don Zack, Harry Quigley, and Alex Kolodkin. Over five years he will acquire expertise in emerging molecular biology and neuroscience techniques required for achieving his long-term goals of: leading an independent high-impact optic nerve regeneration research laboratory, providing outstanding medical and surgical care to patients with glaucoma; and bridging the gap between the clinic and laboratory by helping to usher in a new era of glaucoma treatment though RGC replacement and optic nerve regeneration.
项目摘要/摘要

项目成果

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Thomas Vincent Johnson其他文献

Thomas Vincent Johnson的其他文献

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{{ truncateString('Thomas Vincent Johnson', 18)}}的其他基金

RReSTORE: RGC Repopulation, Stem Cell Transplantation, and Optic Nerve Regeneration.
RReSTORE:RGC 重建、干细胞移植和视神经再生。
  • 批准号:
    10469156
  • 财政年份:
    2022
  • 资助金额:
    $ 18.84万
  • 项目类别:
Visualizing functional retinal integration of transplanted retinal ganglion cells
移植视网膜神经节细胞的功能性视网膜整合可视化
  • 批准号:
    10510837
  • 财政年份:
    2022
  • 资助金额:
    $ 18.84万
  • 项目类别:
Visualizing functional retinal integration of transplanted retinal ganglion cells
移植视网膜神经节细胞的功能性视网膜整合可视化
  • 批准号:
    10707349
  • 财政年份:
    2022
  • 资助金额:
    $ 18.84万
  • 项目类别:
Transplantation of human stem cell-derived neurons for retinal ganglion cell replacement and optic nerve regeneration.
移植人类干细胞衍生的神经元,用于视网膜神经节细胞替代和视神经再生。
  • 批准号:
    10469468
  • 财政年份:
    2020
  • 资助金额:
    $ 18.84万
  • 项目类别:
Transplantation of human stem cell-derived neurons for retinal ganglion cell replacement and optic nerve regeneration.
移植人类干细胞衍生的神经元,用于视网膜神经节细胞替代和视神经再生。
  • 批准号:
    10249198
  • 财政年份:
    2020
  • 资助金额:
    $ 18.84万
  • 项目类别:

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