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干细胞移植拯救了原发性开角型青光眼小鼠模型。

Stem cell transplantation rescued a primary open-angle glaucoma mouse model.

机构信息

Department of Ophthalmology, University of Pittsburgh, Pittsburgh, United States.

Eye Center of Xiangya Hospital, Central South University, Changsha, China.

出版信息

Elife. 2021 Jan 28;10:e63677. doi: 10.7554/eLife.63677.

DOI:10.7554/eLife.63677
PMID:33506763
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7864631/
Abstract

Glaucoma is a leading cause of irreversible blindness. In this study, we investigated if transplanted stem cells are able to rescue a glaucoma mouse model with transgenic myocilin Y437H mutation and explored the possible mechanisms. Human trabecular meshwork stem cells (TMSCs) were intracamerally transplanted which reduced mouse intraocular pressure, increased outflow facility, protected the retinal ganglion cells and preserved their function. TMSC transplantation also significantly increased the TM cellularity, promoted myocilin secretion from TM cells into the aqueous humor to reduce endoplasmic reticulum stress, repaired the TM tissue with extracellular matrix modulation and ultrastructural restoration. Co-culturing TMSCs with myocilin mutant TM cells in vitro promoted TMSCs differentiating into phagocytic functional TM cells. RNA sequencing revealed that TMSCs had upregulated genes related to TM regeneration and neuroprotection. Our results uncovered therapeutic potential of TMSCs for curing glaucoma and elucidated possible mechanisms by which TMSCs achieve the treatment effect.

摘要

青光眼是导致不可逆性失明的主要原因之一。在这项研究中，我们研究了移植的干细胞是否能够拯救具有转基因肌球蛋白 Y437H 突变的青光眼小鼠模型，并探讨了可能的机制。我们将人眼房水生成细胞（TMSCs）通过房水内移植入小鼠眼内，降低了小鼠眼内压，增加了房水流出，保护了视网膜神经节细胞并维持了其功能。TMSC 移植还显著增加了 TM 细胞的数量，促进了 TM 细胞将肌球蛋白分泌到房水中，以减轻内质网应激，通过细胞外基质调节和超微结构修复修复 TM 组织。体外将 TMSCs 与肌球蛋白突变 TM 细胞共培养可促进 TMSCs 分化为具有吞噬功能的 TM 细胞。RNA 测序显示 TMSCs 上调了与 TM 再生和神经保护相关的基因。我们的研究结果揭示了 TMSCs 治疗青光眼的治疗潜力，并阐明了 TMSCs 实现治疗效果的可能机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/73be/7864631/df06c0578181/elife-63677-fig10.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/73be/7864631/df06c0578181/elife-63677-fig10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/73be/7864631/8af153481144/elife-63677-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/73be/7864631/064cd8b898cb/elife-63677-fig1-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/73be/7864631/38f201f93808/elife-63677-fig1-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/73be/7864631/31bc124f7c16/elife-63677-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/73be/7864631/b393c1f94803/elife-63677-fig2-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/73be/7864631/d0378c28916c/elife-63677-fig3.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/73be/7864631/8f941ac01234/elife-63677-fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/73be/7864631/49f5d1498552/elife-63677-fig7-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/73be/7864631/e86a8d876f43/elife-63677-fig8.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/73be/7864631/df06c0578181/elife-63677-fig10.jpg

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