DIFFERENTIAL GENE EXPRESSION IN CILIARY EPITHELIUM

描述：眼睫毛上皮是神经上皮的双层结构。 具有神经内分泌表型特征的细胞。该表达式由 睫状体上皮编码神经肽加工酶的基因， 仅限于神经内分泌的神经肽、多肽激素和受体 组织建立了我们观察的分子基础，即这只眼睛 组织具有神经内分泌功能。私家侦探提出了假设 在眼睛的前段，睫状体上皮是 神经肽和多肽激素合成的主要部位(即， 神经降压素、心钠素、血管紧张素原)已知 心血管系统中的高血压/降压作用，以及 在调节眼压方面的潜在作用。他建议， 睫状体上皮通过内分泌机制调节眼压 (自分泌/旁分泌)通过作用于内流的调节肽 系统[无色素(NPE)和色素睫状上皮细胞(PE)]， 和/或流出系统[小梁网络细胞(TM)]。 本研究的主要实验方法是：1)研究 在人的睫状体上皮细胞中，参与 生物活性的基因表达、合成、加工和信号通路 多肽及其受体在高血压/低血压中的作用 在正常和青光眼中。2)使用已建立的细胞系衍生 从流入系统(即NPE、PE)和流出系统(即小梁 网络)，作为定义神经内分泌的体外细胞模型系统 睫状体上皮的特性。3)减法的运用 人睫状体新候选基因的杂交法研究 与高眼压/低眼压性青光眼有关。具体的 目的如下：1)确定《公约》的表述规则 内切酶(前激素转换酶)和外肽酶(羧基肽酶) 和多肽甘氨酸(-酰胺化单加氧酶)参与加工 神经肽和肽激素；2)基因表达的特征 具有降压/降压作用的调节肽及其受体； 3)确定成熟和成熟所涉及的调控机制 正常和青光眼患者加工酶和神经肽的分泌 4)决定信号转导途径。 参与调节的受体激活的途径 NPE/PE和TM细胞中的多肽；5)决定结构和功能 编码TIGR、a的人睫状体消减克隆的关系 参与青光眼(青少年开角型青光眼)亚群的蛋白质和 调节眼压的候选基因。

DESCRIPTION: The ocular ciliary epithelium is a bilayer of neuroepithelial cells with a characteristic neuroendocrine phenotype. The expression by the ciliary epithelium of genes encoding neuropeptide processing enzymes, neuropeptides, peptide hormones and receptors restricted to neuroendocrine tissues establishes the molecular basis of our observations that this ocular tissue displays neuroendocrine functions. The PI formulated the hypothesis that, in the anterior segment of the eye, the ciliary epithelium is the primary site of synthesis of neuropeptides and peptide hormones (i.e., neurotensin, atrial natriuretic peptide, angiotensinogen) of known hypertensive/hypotensive actions in the cardiovascular system, and with potential roles in the regulation of eye pressure. He proposes that the ciliary epithelium modulates eye pressure by endocrine mechanisms (autocrine/paracrine) through regulatory peptides acting on the inflow system [nonpigmented (NPE) and pigmented ciliary epithelial cells (PE)], and/or on the outflow system [trabecular meshwork cells (TM)]. The major experimental approach of this research will be: 1) to investigate in the human ciliary epithelium, the molecular mechanism involved in the gene expression, synthesis, processing and signaling pathways of bioactive peptides and its receptors with putative roles in hypertension/ hypotension in normal and glaucoma eyes. 2) The use of established cells lines derived from the inflow system (i.e., NPE, PE) and outflow (i.e., trabecular meshwork), as in vitro cell model systems to define the neuroendocrine properties of the ciliary epithelium. 3) The application of subtractive hybridization to identify novel candidate genes in the human ciliary body associated to high intraocular pressure/low tension glaucoma. The specific aims are as follows: 1) Determine the regulation of the expresssion of endoproteases (prohormone convertases), and exopeptidases (carboxypeptidases and peptidylglycine (-amidating monooxygenase) involved in the processing of neuropeptides and peptide hormones; 2) Characterize the gene expression of regulatory peptides with hypertensive/hypotensive actions and its receptors; 3) Determine the regulatory mechanism involved in the maturation and secretion of processing enzymes and neuropeptides in normal and glaucoma derived ciliary epithelial cells; 4) Determine the signal transduction pathways involved upon activation of the receptors for the regulatory peptides in NPE/PE and TM cells; 5) Determine the structure-function relationship of a human ciliary body subtracted clone encoding TIGR, a protein involved in a subset of glaucoma (Juvenile Open Angle Glaucoma) and a candidate gene to regulate eye pressure.