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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.