Cell-Mediated Inflammatory Pathway and Diabetic Retinopathy-Administrative Supplement

摘要： 视网膜周细胞是与血管内皮细胞相邻并为其提供支持的收缩细胞。 毛细血管，在调节眼睛的视网膜血管系统中是必不可少的。早期阶段 糖尿病视网膜病变的特征是视网膜周细胞的丢失，这导致 包括血管生成在内的晚期病理学的发展。尽管我们知道的很多 关于糖尿病视网膜病变的病因，即刺激视网膜周细胞丢失的凋亡途径 目前仍不清楚。我们的初步研究表明，单核细胞来源的巨噬细胞分泌 转化生长因子β1，诱导转化生长因子β1诱导的促凋亡的BIGH3的表达和分泌 蛋白(转化生长因子β诱导的基因人克隆3)诱导内皮细胞凋亡和 视网膜周细胞。这一系列事件被归因于视网膜的主要原因 周细胞凋亡与糖尿病视网膜病变。巨噬细胞转化生长因子-β-1和BIGH3是糖尿病前期 糖尿病视网膜病变的生物标志物和潜在治疗靶点 个人。在目前的研究中，我们假设类似的巨噬细胞-转化生长因子β-BIGH3 该通路可诱导视网膜周细胞发生凋亡。我们将研究它们之间的相互作用 内皮细胞和视网膜周细胞以及巨噬细胞在视网膜周细胞表达中的作用 BIGH3对转化生长因子β的反应，以及视网膜周细胞的凋亡。此外，我们还将研究 BIGH3与跨膜信号蛋白受体整合素的结合及其作用 以介导视网膜周细胞的凋亡。这项新的研究集中在巨噬细胞介导的 影响糖尿病视网膜病变的分子途径及其治疗机会 对这种眼科疾病的干预。受训学生将参与这些研究 项目，提供生物医学研究方面的宝贵经验。

Abstract: Retinal pericytes are contractile cells adjacent to and provide support for endothelial cells of capillaries, which are essential in the regulation of retinal vasculature in the eye. Early stages of diabetic retinopathy are characterized by the loss of retinal pericytes, which lead to the development of advanced-stage pathology including angiogenesis. Although much is known about the etiology of diabetic retinopathy, the apoptotic pathway that incites retinal pericyte loss remains unclear. Our preliminary studies reveal that monocyte-derived macrophages secrete TGFβ1, which induces the expression and secretion of a TGFβ1-Induced, pro- apoptotic BIGH3 protein (TGFβ –Induced Gene Human Clone 3) leading to apoptosis of endothelial cells and retinal pericytes. This cascade of events has been attributed to the primary cause of retinal pericyte apoptosis and diabetic retinopathy. Macrophage TGF-β1 and BIGH3 are prediabetic biomarkers, and potential therapeutic targets for intervention of diabetic retinopathy for diabetic individuals. In the present study, we hypothesize that a similar macrophage-TGFβ–BIGH3 pathway may induce apoptosis in retinal pericytes. We will investigate the interaction between endothelial cells and retinal pericytes, as well as macrophages’ role on retinal pericyte expression of BIGH3 in response to TGFβ, and retinal pericyte apoptosis. Furthermore, we will also study the association of BIGH3 with integrin, a trans-membrane signaling protein receptor and its role to mediate retinal pericyte apoptosis. This novel study focuses on macrophage-mediated molecular pathway to impact diabetic retinopathy and it will provide opportunities of therapeutic intervention of this ocular eye disorder. Student trainees will be involved in these research projects, providing valuable experience on biomedical research.