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A zebrafish model for studying orbital development and disease

用于研究眼眶发育和疾病的斑马鱼模型

基本信息

批准号：
8204650
负责人：
Alon Kahana
金额：
$ 21.66万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-01-01 至 2012-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8204650
关键词：
Adipocytes Adult Affect American Anatomy Animal Model Antisense Oligonucleotides Behavior Biological Biological Models Biology Blindness Cells Cellular biology Chronic Cicatrix Compartment syndromes Congenital Heart Defects Cornea Defect Development DiGeorge Syndrome Diagnosis Diagnostic Diplopia Disease Embryology Embryonic Development Exophthalmos Eye Eye Development Eye diseases Fatty acid glycerol esters Fetal Alcohol Syndrome Fibroblasts Fibrosis Fluorescent Dyes Forms Controls Genes Genetic Genetic Markers Glaucoma Goals Headache Hyaluronan Immunohistochemistry In Situ Hybridization Inflammatory Injection of therapeutic agent Lead Light Mediating Messenger RNA Molecular Genetics Muscle Neural Crest Neural Crest Cell Ocular orbit Operative Surgical Procedures Orbital Diseases Pain Pathogenesis Pathology Pathway interactions Patients Pattern Population Process Proliferating Proteins Public Health Quality of life Research Research Project Grants Risk Signal Pathway Signal Transduction Skin Steroids Study models Swelling Techniques Testing Thyroid Diseases Thyroid Gland Thyroid Hormones Time Tissues Transgenic Organisms Zebrafish autoimmune thyroid disease cell type eye dryness eye transplantation improved insight lipid biosynthesis melanoma migration novel ocular neurofibromatosis optic nerve disorder orbit muscle overexpression productivity loss promoter research study stem cell population tool

项目摘要

Thyroid-related eye disease (TED) is an important public health burden that causes loss of productivity and reduces quality of life. TED can lead to chronic debilitating pain and headaches, double vision, corneal exposure, dry eyes, secondary glaucoma and compressive optic neuropathy, and carries a significant risk of vision loss. The pathogenesis of TED is incompletely understood, but involves the activation of orbital fibroblasts by an unidentified thyroid-related cell signal. Activated fibroblasts in turn secrete large quantities of hyaluronan, causing significant swelling of orbital tissues and especially extraocular muscles. In addition, orbital fibroblasts mediate a severe inflammatory orbitopathy that leads to orbital fibrosis. Orbital fibroblasts can also proliferate and differentiate into adipocytes, filling the orbit with excess fat. The combination of tissue swelling, scarring and adipogenesis leads to exophthalmos and a compartment syndrome whereby normal orbital tissues are compressed by the abnormal ones, leading to compressive optic neuropathy, secondary glaucoma and chronic orbital headaches. Exophthalmos can lead to chronic dry eyes and corneal exposure. The swelling and fibrosis of muscles can lead to ocular misalignment and diplopia. Orbital fibroblasts are derivatives of the neural crest, a transient population of pluripotent cells that differentiate into a broad range of tissues during embryogenesis. The unique behavior of orbital fibroblasts in TED may be partially caused by their embryologic neural crest origins. The main hypothesis of this project is that embryologic processes that occur during the development of the orbital neural crest are important in the pathogenesis of TED. The biology of the orbital neural crest is unknown and largely unexplored. The goal of this research project is to utilize the genetic and cell biology tools available in zebrafish to shed new light on the genetics and cell biology of orbital neural crest-derived tissues, in order to lead to improved diagnostic and treatment for TED and other orbital diseases. Thyroid-related eye disease is an important public health burden that causes loss of productivity anda reduced quality of life.Thegoal of this research is to utilize the genetic and cell biology tools available in zebrafish (a vertebrate model system) to shed new light on the biology of orbital neural crest-derived tissues, in order to lead to improved diagnosis and treatment for TEDand other orbital diseases.

甲状腺相关眼病（TED）是一种重要的公共卫生负担，生产力，降低生活质量。TED会导致慢性衰弱性疼痛和头痛，而且是双重的视力，角膜暴露，干眼，继发性青光眼和压迫性视神经病变，并携带视力丧失的重大风险。TED的发病机制尚不完全清楚，但涉及未识别的甲状腺相关细胞信号激活眼眶成纤维细胞。依次激活成纤维细胞分泌大量透明质酸，导致眼眶组织显著肿胀，眼外肌此外，眼眶成纤维细胞介导严重的炎性眼眶病，导致眼眶纤维化眼眶成纤维细胞也可以增殖并分化成脂肪细胞，多余的脂肪组织肿胀、瘢痕形成和脂肪形成的结合导致眼球突出和筋膜室综合征，其中正常的眼眶组织被异常的眼眶组织压迫，导致压迫性视神经病变、继发性青光眼和慢性眼眶头痛。眼球突出会导致慢性干眼症和角膜暴露。肌肉的肿胀和纤维化可导致眼部失准和复视。眼眶成纤维细胞是神经嵴的衍生物，神经嵴是多能细胞的短暂群体，在胚胎发生过程中分化成各种组织。眼眶成纤维细胞的独特行为 TED可能部分由其胚胎神经嵴起源引起。这个项目的主要假设是在眶神经嵴发育过程中发生的胚胎学过程在 TED的发病机制眶神经嵴的生物学是未知的，而且大部分未被探索。的目标该研究项目是利用斑马鱼的遗传和细胞生物学工具，眼眶神经嵴衍生组织的遗传学和细胞生物学，以改善诊断以及TED和其他眼眶疾病的治疗。甲状腺相关眼病是一种重要的公共卫生负担，会导致生产力下降，这项研究的目标是利用遗传和细胞生物学工具，斑马鱼（一种脊椎动物模型系统）为眼眶神经嵴衍生组织的生物学提供了新的线索，以改善TED和其他眼眶疾病的诊断和治疗。

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

The eye as an organizer of craniofacial development.

DOI：
10.1002/dvg.20716
发表时间：
2011-04
期刊：
GENESIS
影响因子：
1.5
作者：
Kish, Phillip E.;Bohnsack, Brenda L.;Gallina, Donika;Kasprick, Daniel S.;Kahana, Alon
通讯作者：
Kahana, Alon

Nonophthalmic symptoms secondary to ocular torticollis from severe blepharoptosis: an underappreciated but treatable condition.

严重上睑下垂引起的眼部斜颈继发的非眼科症状：一种未被充分认识但可以治疗的疾病。