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Role of plasmacytoid dendritic cells in corneal nerve health and regeneration

浆细胞样树突状细胞在角膜神经健康和再生中的作用

基本信息

批准号：
9208776
负责人：
Pedram Hamrah
金额：
$ 20.63万
依托单位：
TUFTS MEDICAL CENTER
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：
2016-02-01 至 2018-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9208776
关键词：
Adoptive Transfer Affect Anatomy Anterior Biological Preservation Bone Marrow Brain-Derived Neurotrophic Factor Burr hole procedure Cell physiology Cells Coculture Techniques Cornea Corneal Stroma Critical Pathways Dendritic Cells Development Diphtheria Toxin Disease Enzyme-Linked Immunosorbent Assay Epithelial Esthesia Eye Eye diseases Family Fiber Flow Cytometry Functional disorder GDNF gene Health Herpetic Keratitis Immune Immunofluorescence Immunologic Inflammatory Injection of therapeutic agent Keratitis Knowledge Link Maintenance Measures Mediating Messenger RNA Modeling Morbidity - disease rate Morphology Mus Myelogenous Natural regeneration Nerve Nerve Fibers Nerve Growth Factors Nerve Plexus Nerve Regeneration Nervous System Trauma Neurites Neurodegenerative Disorders Neurons Neuropeptide Receptor Pathologic Peripheral Nervous System Diseases Play Process Property Protein Tyrosine Kinase Proteins Quantitative Reverse Transcriptase PCR Recovery of Function Regulation Role Sensory Signal Transduction Somatostatin Receptor Source Staining method Stains Structure of trigeminal ganglion Tachykinin Receptor Time Tissues Transgenic Organisms Transplanted tissue Trigeminal nerve structure Tubulin VIPR2 protein Vision Wild Type Mouse Wound Healing adaptive immune response blink reflexes density eye dryness glial cell-line derived neurotrophic factor immune function in vivo intravenous injection macrophage melanocortin receptor nerve injury nerve supply neurotrophic factor neurotrophin 4 novel therapeutic intervention novel therapeutics ocular surface prevent public health relevance receptor reconstitution tumor vasoactive intestinal peptide 2 receptor

项目摘要

DESCRIPTION (provided by applicant): Corneal nerve dysfunction is the pathophysiologic basis of many ocular surface diseases, causing considerable morbidity, including neurotrophic keratitis and dry eye disease and therefore corneal nerve health is a prerequisite for the maintenance of vision. Despite the traditional point of view that immune cells are deleterious for nerve regeneration, recent evidence suggests that immune cells can show beneficial effects in neuronal regeneration. For instance, macrophages and conventional dendritic cells are among the key players in providing a neuro-protective and neuro-trophic microenvironment for nerve regeneration following nerve damage. Despite recent evidence on neuro-protective and neuro-regenerative functions of immune cells, the role and source of endogenous neurotrophic molecules in the cornea remains elusive. Moreover, the impact of recently identified plasmacytoid dendritic cells (pDCs), a vital subset of immune cells that reside in the anterior stroma just beneath sub-basal corneal nerve plexus of cornea, remains to be determined. These cells orchestrate and link innate and adaptive immune responses and are implicated in the induction of tolerance to transplanted tissues or tumors. Our preliminary results suggest that pDCs are vital in the maintenance and function of corneal nerves, as we demonstrate that local depletion of pDCs in the cornea leads to abrupt and severe nerve loss and diminishment of corneal sensation. Our hypothesis is that pDCs contribute to maintenance, function, and regeneration of nerves through secretion of neurotrophic molecules. Our specific aims include evaluating the significance of pDCs on corneal nerve maintenance and health as well as studying the impact of pDCs on neural regeneration in the cornea following nerve damage. Our fresh perspective on how pDCs contribute to regulation of corneal nerve microenvironment holds promise of amplifying our knowledge far beyond the current state on the cross talk between nerve fibers and immune cells in the cornea and the impact of such cross talk on corneal nerve health and function. Furthermore, this application suggests in vivo approaches for assessing significance of corneal pDCs, in nerve protection and regeneration. Therefore, this proposal will elucidate the neuro-protective and neuro-regenerative properties of pDCs, may result in novel therapeutic approaches, and is potentially applicable in tissues other than cornea and conditions in which neuro-regeneration is vital, including traumatic nervous system injuries, neurodegenerative diseases, and peripheral neuropathies.