A zebrafish model for studying orbital development and disease

甲状腺相关眼病(TED)是一种重要的公共卫生负担，导致 提高生产力，降低生活质量。TED会导致慢性衰弱的疼痛和头痛，加倍 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 有严重的失明风险。TED的发病机制尚不完全清楚，但涉及 一种不明的甲状腺相关细胞信号激活眼眶成纤维细胞。依次激活的成纤维细胞 分泌大量透明质酸，导致眼眶组织显著肿胀，尤其是 眼外肌。此外，眼眶成纤维细胞介导严重的炎症性眼眶病变，导致 眼眶纤维化。眼眶成纤维细胞也可以增殖和分化为脂肪细胞，使眼眶充满 脂肪过多。组织肿胀、疤痕形成和脂肪生成共同导致眼球突出和 间隔综合征，即正常的眼眶组织被异常的眼眶组织压缩，导致 压迫性视神经病变、继发性青光眼和慢性眼眶头痛。眼球突出可导致 到慢性干眼症和角膜暴露。肌肉的肿胀和纤维化可导致眼球 错位和复视。 眼眶成纤维细胞是神经脊的衍生品，神经脊是一种瞬时的多能细胞群体，它 在胚胎发育过程中分化成广泛的组织。眼眶成纤维细胞的独特行为 TED可能部分是由胚胎性神经脊起源引起的。这个项目的主要假设是 在眼眶神经脊发育过程中发生的胚胎学过程在 TED的发病机制。眼眶神经脊的生物学还不为人所知，而且在很大程度上还没有被探索过。的目标是 这项研究项目旨在利用斑马鱼中可用的遗传和细胞生物学工具来揭示 眼眶神经脊源性组织的遗传学和细胞生物学，以提高诊断水平 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，会导致生产力和 降低生活质量。这项研究的目标是利用 斑马鱼(一种脊椎动物模型系统)为眼窝神经脊源性组织的生物学提供了新的线索， 以改进对TED和其他眼眶疾病的诊断和治疗。

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.