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：
9250155
负责人：
Deepak Ashok Lamba
金额：
$ 48.5万
依托单位：
BUCK INSTITUTE FOR RESEARCH ON AGING
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 2018-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9250155
关键词：
Accounting Acute Affect Apoptosis Astrocytes Blindness Cell Death Cell Transplants Cells Clinic Clinical Trials Cytoprotection Data Degenerative Disorder Development Direct Costs Disease Disease Progression Dopamine Dopaminergic Cell Drosophila genus Environment Goals Hemocytes Homologous Gene Immune Immune Cell Activation Immunologic Tests Inherited Injection of therapeutic agent 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 Recruitment Activity Regenerative Medicine Regulation Replacement Therapy Retina Retinal Retinal Degeneration Retinal Diseases Retinal Photoreceptors Role Societies Source Stem cells 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 improved induced pluripotent stem cell insight macrophage monocyte mouse model neuroprotection neurotrophic factor novel therapeutic intervention paracrine photoreceptor degeneration prevent public health relevance regenerative repaired response retinal damage 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（由适用提供）：与神经系统的许多其他区域一样，视网膜受到各种遗传和获得的退化条件。这些条件通常会导致感光体的变性，即视网膜中的主要光感应细胞。尽管受感受器的失去损失，但内部视网膜电路已完整多年，这导致可能将光感受器置换为潜在的治疗。细胞替代策略很重要，因为哺乳动物视网膜中感光体的丧失与居民细胞的任何有效再生无关。细胞置换的潜在来源可能是多能干细胞。有许多小组研究了干细胞得出的RPE的潜力，其中包括批准的临床试验，用于替换AMD和Stargardt营养不良的RPE细胞。但是，随着疾病的视力丧失的发展，患者也需要替换失去的感光细胞。尽管许多组已经显示了小鼠视网膜中光感受器的整合，但总体效率确实很低。此外，小胶质细胞在此过程中的作用在很大程度上是意外的。该建议旨在研究小胶质细胞衍生的神经营养因素在视网膜修复和再生医学中的作用。我们将使用跨物种方法来识别和进行基础研究，并将结果应用于哺乳动物的视网膜。