亚临床甲减(SCH)等引起的促甲状腺激素（TSH）增高可能是引起大血管病变如动脉粥样硬化的原因。TSH是垂体分泌的生长类激素，参与细胞的增殖与分化。课题组曾报道，TSH升高的患者糖尿病视网膜病变发生及进展明显增加，特别是威胁视力的视网膜病变，其机制可能与TSH升高促进血管内皮的增殖分化有关。预实验证实视网膜组织及血管内皮细胞有TSHR的表达，但尚不清楚其在视网膜血管发生中的作用机制。本课题拟在动物水平上：选择氧诱导小鼠视网膜新生血管模型，给予高TSH及甲状腺激素干预，研究视网膜新生血管及血管生成相关基因及蛋白表达变化；在细胞水平上：通过高TSH、TSHR敲减等观察其对细胞增殖与分化的影响；并应用数字化表达谱测序技术研究增殖相关信号通路的激活情况。TSH及甲状腺激素在视网膜新生血管中的作用机制的研究，将为临床治疗SCH以预防视网膜病变发生发展提供理论依据。

Increased thyrotropin (TSH), caused by subclinical hypothyroidism (SCH), is associated with macrovascular disease, such as atherosclerosis. The roles of TSH in cellular proliferation and differentiation have been documented. Our previous studies have found that SCH was associated with greater prevalence and development of diabetic retinopathy, especially sight-threatening diabetic retinopathy. It may be associated with the increased proliferation and differentiation of vascular cells. TSH receptor is proved to be expressed in the retina and vascular endothelial cells in our preliminary experiment. However, the mechanisms of thyroid hormone in retinal vascular development are not well known. We intended to evaluate the effects of L-thyroxine and recombinant thyrotropin on the development of oxygen-induced retinopathy in neonatal mice. 84 genes involved in angiogenesis and retinal neovascularization were analyzed. In addition, we intended to explore the effects of thyroid hormone, recombinant TSH and knockdown TSH receptor on the proliferation and differentiation of vascular endothelial cells and associated cellular signal transduction pathway by sequencing technology of digital expression profiles. Investigating the mechanisms of thyroid hormone and TSH on the development of retinal neovascularization might provide theoretical basis for clinical treating SCH to prevent the occurrence and development of retinopathy.