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Investigation of factors that prevent endogenous regeneration of the retina by Müller stem cells

阻止 Müller 干细胞视网膜内源性再生的因素的研究

基本信息

批准号：
MR/K008722/1
负责人：
Gloria Limb
金额：
$ 4.55万
依托单位：
University College London
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2013
资助国家：
英国
起止时间：
2013 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=MR%2FK008722%2F1
关键词：
Investigation factors prevent endogenous regeneration

项目摘要

Adult human retina harbours a population of Müller cells with stem cell characteristics. Although these cells have the ability to grow and neurally differentiate in vitro, there is no evidence that they regenerate retina in vivo. It has been thought that factors released during reactive gliosis, a glial proliferation observed in all retinal degenerative conditions, are responsible for the inhibition of retinal regeneration by endogenous stem cells. The proposed research aims to identifiy factors that may promote neural regeneration of diseased retina by stimulating the endogenous proliferation and neural differentiation of Müller stem cells. Using proteomic approaches, we will investigate the total protein and cytokine expression profile of fragments of human gliotic retina, surgically removed as part of the treatment for complicated retinal detachment, and will compare this profile with that of normal cadaveric donor retina. Factors found to be selectively increased or decreased in degenerated retina will then be examined for their ability to inhibit or promote Müller stem cell growth and differentiation in vitro. Once candidate factors have been found to be active on the inhibition or promotion of these cell functions, we will confirm their roles by blocking or promoting their activities using agonist or antagonist molecules for these factors. The work will be undertaken in collaboration with Prof. Sun Xinghai and Dr Lei Yuan from the Eye Hospital at Fudan University, Shanghai. The proteomic analysis will be performed at the UCL Institute of Ophthalmology and is expected to identify candidate factors which can be examined by both the UK and the Fudan group on Müller stem cell growth and differentiation. The project will form part of a PhD training program for a Chinese student who will visit the UCL Institute of Ophthalmology for a year. Funding for her visit and that of Prof Sun and Dr Lei, her PhD supervisors, is being sought by the Fudan University group from the Natural Science Foundation of China.

成年人视网膜含有具有干细胞特征的Müller细胞群。虽然这些细胞在体外具有生长和神经分化的能力，但没有证据表明它们在体内再生视网膜。人们认为，在反应性神经胶质增生（在所有视网膜变性疾病中观察到的神经胶质增生）期间释放的因子是内源性干细胞抑制视网膜再生的原因。该研究旨在通过刺激Müller干细胞的内源性增殖和神经分化来确定可能促进患病视网膜神经再生的因素。使用蛋白质组学的方法，我们将调查总蛋白和细胞因子的表达谱的片段的人胶质视网膜，手术切除的复杂的视网膜脱离的治疗的一部分，并将此配置文件与正常的尸体供体视网膜。然后将检查在变性视网膜中发现的选择性增加或减少的因子在体外抑制或促进Müller干细胞生长和分化的能力。一旦发现候选因子对这些细胞功能的抑制或促进具有活性，我们将通过使用这些因子的激动剂或拮抗剂分子阻断或促进其活性来确认其作用。这项工作将与上海复旦大学眼科医院的孙星海教授和雷媛博士合作进行。蛋白质组学分析将在伦敦大学学院眼科研究所进行，预计将确定英国和复旦大学研究小组可以对Müller干细胞生长和分化进行检测的候选因子。该项目将成为一名中国学生博士培训项目的一部分，该学生将访问伦敦大学学院眼科研究所一年。复旦大学的研究小组正向中国自然科学基金委员会寻求资助，以资助她及其博士生导师孙教授和雷博士的访问。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Comparison of proteomic profiles in the zebrafish retina during experimental degeneration and regeneration.

DOI：
10.1038/srep44601
发表时间：
2017-03-16
期刊：
Scientific reports
影响因子：
4.6
作者：
Eastlake K;Heywood WE;Tracey-White D;Aquino E;Bliss E;Vasta GR;Mills K;Khaw PT;Moosajee M;Limb GA
通讯作者：
Limb GA

Optimized feline vitrectomy technique for therapeutic stem cell delivery to the inner retina.

DOI：
10.1111/vop.12160
发表时间：
2014-07
期刊：
Veterinary ophthalmology
影响因子：
1.6
作者：
Jayaram H;Becker S;Eastlake K;Jones MF;Charteris DG;Limb GA
通讯作者：
Limb GA

Müller glia as an important source of cytokines and inflammatory factors present in the gliotic retina during proliferative vitreoretinopathy.

DOI：
10.1002/glia.22942
发表时间：
2016-04
期刊：
Glia
影响因子：
6.2
作者：
Eastlake K;Banerjee PJ;Angbohang A;Charteris DG;Khaw PT;Limb GA
通讯作者：
Limb GA

Allogeneic Transplantation of Müller-Derived Retinal Ganglion Cells Improves Retinal Function in a Feline Model of Ganglion Cell Depletion.

DOI：
10.5966/sctm.2015-0125
发表时间：
2016-02
期刊：
Stem cells translational medicine
影响因子：
6
作者：
Becker S;Eastlake K;Jayaram H;Jones MF;Brown RA;McLellan GJ;Charteris DG;Khaw PT;Limb GA
通讯作者：
Limb GA

Comparative proteomic analysis of normal and gliotic PVR retina and contribution of Müller glia to this profile.

DOI：
10.1016/j.exer.2018.08.016
发表时间：
2018-12
期刊：
Experimental eye research
影响因子：
3.4
作者：
Eastlake K;Heywood WE;Banerjee P;Bliss E;Mills K;Khaw PT;Charteris D;Limb GA
通讯作者：
Limb GA