Enhancing photoreceptor integration using microglia-derived secreted factors

使用小胶质细胞衍生的分泌因子增强光感受器整合

基本信息

批准号：
9903319
负责人：
Deepak Ashok Lamba
金额：
$ 40.31万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-04-01 至 2021-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9903319
关键词：
Accounting Acute Affect Apoptosis Astrocytes Blindness Cell Death Cell Transplantation Cells Clinic Clinical Trials Cytoprotection Data Degenerative Disorder Development Direct Costs Disease Disease Progression Dopamine Dopaminergic Cell Drosophila genus Environment Financial Hardship Goals Hemocytes Homologous Gene Immune Immunologic Tests Inherited Injections Light Mammals Microglia Modeling Morphology Mus Natural regeneration Nervous system structure Neurons Parkinson Disease Patients Phenotype Photoreceptors Platelet-Derived Growth Factor Pluripotent Stem Cells Process Protocols documentation Recovery Regenerative Medicine Regulation Replacement Therapy Retina Retinal Degeneration Retinal Diseases Retinal Photoreceptors Role Societies Source Testing Therapeutic Time Tissues Transplantation UV induced Ultraviolet Rays Vascular Endothelial Growth Factors Vision Work autocrine base experimental study fly functional restoration genetic approach human disease human embryonic stem cell human embryonic stem cell transplantation immune activation improved induced pluripotent stem cell insight macrophage monocyte mouse model neuroprotection neurotrophic factor novel therapeutic intervention paracrine photoreceptor degeneration prevent public health relevance recruit regenerative repaired response retinal damage stem cells success tissue regeneration tissue repair ultraviolet damage

项目摘要

DESCRIPTION (provided by applicant): The retina, like many other regions of the nervous system, is subject to a variety of inherited and acquired degenerative conditions. These conditions often result in the degeneration of the photoreceptors, the main light sensing cells in the retina. Despite the loss of photoreceptors, the inner retinal circuitry is intact for many year, and this has led to the possibility of photoreceptor replacement as a potential therapy. Cell replacement strategy is important as the loss of photoreceptors in the mammalian retina is not associated with any effective regeneration from resident cells. A potential source of cellular replacement could be pluripotent stem cells. There are a number of groups looking into the potential of stem cell derived RPE including an approved clinical trial for RPE cell replacement for AMD and Stargardt dystrophy. However, as the disease progresses to vision loss, patients will require replacement of the lost photoreceptor cells as well. Although a number of groups have shown integration of photoreceptors in the mouse retina, the overall efficiency is really low. Additionally, the role of the microglia in this process has largely been unexplored. This proposal aims to look at the role of microglia-derived neurotrophic factors in both retinal repair and regenerative medicine. We will use a cross-species approach to identify and carry out basic studies in flies and apply the result in mammalian retinas.

描述（由申请人提供）：与神经系统的许多其他区域一样，视网膜会遭受各种遗传性和后天性退化状况的影响，这些状况通常会导致感光细胞（视网膜中主要的感光细胞）退化。尽管光感受器丧失，但视网膜内部电路多年来仍保持完整，这使得光感受器替代成为一种潜在疗法的可能性，因为细胞替代策略非常重要，因为光感受器的丧失。哺乳动物视网膜与驻留细胞的任何有效再生无关，细胞替代的潜在来源可能是多能干细胞，有许多小组正在研究干细胞衍生的 RPE 的潜力，其中包括一项已批准的 RPE 细胞替代临床试验。然而，随着疾病进展到视力丧失，患者也需要更换丢失的感光细胞，尽管许多研究小组已经证明小鼠视网膜中存在感光细胞整合，但总体效率较高。确实很低。此外，小胶质细胞在此过程中的作用很大程度上尚未被探索，该提案旨在研究小胶质细胞衍生的神经营养因子在视网膜修复和再生医学中的作用。对果蝇的基础研究并将结果应用于哺乳动物视网膜。

项目成果

期刊论文数量（2）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Small Molecule-Based Retinal Differentiation of Human Embryonic Stem Cells and Induced Pluripotent Stem Cells.

基于小分子的人胚胎干细胞和诱导多能干细胞的视网膜分化。

DOI：
发表时间：
2018-06-20
期刊：
影响因子：
0.8
作者：
Zhu, Jie;Lamba, Deepak A
通讯作者：
Lamba, Deepak A

Generation of Transplantable Retinal Photoreceptors from a Current Good Manufacturing Practice-Manufactured Human Induced Pluripotent Stem Cell Line.

从当前良好生产规范制造的人类诱导多能干细胞系中产生可移植的视网膜感光器。

DOI：
发表时间：
2018-02
期刊：
影响因子：
6
作者：
Zhu, Jie;Reynolds, Joseph;Garcia, Thelma;Cifuentes, Helen;Chew, Shereen;Zeng, Xianmin;Lamba, Deepak Ashok
通讯作者：
Lamba, Deepak Ashok