结缔组织生长因子在糖尿病视网膜病变中的调控机制及研究进展

糖尿病视网膜病变是一种微血管循环异常的致盲性眼病。在疾病进展后期，血管内皮生长因子抗体类药物因可显著抑制新生血管形成和改善黄斑水肿而被广泛应用于临床。然而，药物应用后纤维化趋势的加重也引起了广泛的关注。结缔组织生长因子作为眼内纤维化的重要细胞因子，在药物应用后过量表达，被认为是引起上述副反应的重要因素之一，也是一种潜在的辅助治疗靶点。整理目前研究进展后发现，结缔组织生长因子的调控机制包括调控下游细胞因子基因表达和直接结合于其他细胞因子或受体两种方式。因其特殊的四模块结构上具有多种细胞因子特异结合位点，其调控方式多依赖于后者，进而促进或抑制了多种重要细胞因子通路的表达。在糖尿病视网膜病变中，其表达贯穿整个疾病进程。在临床前期和新生血管形成末期，结缔组织生长因子的累积分别起到促进基底膜增厚和新生血管纤维化形成的重要作用。本文将对结缔组织生长因子多样化的调控机制及该因子在DR中的研究进展进行系统阐述。

Regulatory mechanism and research progress of connective tissue growth factor in diabetic retinopathy

Diabetic retinopathy is one of the microvascular abnormal diseases. In the late stage of disease progression, the antibody of vascular endothelial growth factor can significantly inhibit the formation of new blood vessels and improve macular edema, which is widely used in clinical. However, the aggravation of pro-fibrotic influence after long-term treated by the medicine also attracts a wide range of attention. Connective tissue growth factor, as an important cytokine in intraocular fibrosis, over expressed after treated by the drug, is considered to be one of the most important factors in the side effect of the drug, and is also a potential therapeutic target. After finishing the current research, the regulation mechanism of connective tissue growth factor, includes two ways, regulation of gene expression and direct binding to other cell factors or receptors. Because of its special four module structure, it has many kinds of cell factor specific binding sites, and its regulation mode is more dependent on the latter, which promotes or inhibits the expression of several important cytokine pathways. In diabetic retinopathy, its expression goes throughout the disease process. The accumulation of connective tissue growth factor plays an important role in promoting the thickening of basement membrane and the formation of new blood vessels in the early stage of the clinical stage and the formation of the new blood vessels. In this paper, the regulatory mechanism of connective tissue growth factor and the research progress of this factor in DR are systematically expounded.