AQUAPORIN WATER CHANNEL PROTEINS IN EYE

水穿过质膜的运动对于细胞的生长至关重要。 眼内几种组织的功能。 然而，分子 负责水运输的结构一直是个谜， 最近发现的CHIP（AQP 1）和水通道蛋白的其他成员 膜水通道蛋白家族。 多种水通道蛋白 在眼内鉴定：AQP 1存在于无色素睫状体上皮， 角膜内皮、透镜上皮和小梁网; AQP 5主要分布于角膜上皮、泪腺和唾液腺; AQP 6存在于视网膜色素上皮细胞中。 对这些蛋白质的分析可以 现在提供分子洞察水运输在正常视力 以及几种眼病。 I.基因研究。 将对人、鼠和牛的AQP 5 cDNA进行测序。 分离并比较可能重要的残基的保存 为了发挥功能，将从人和小鼠中克隆AQP 5基因。 基因组文库，它们的组织，拷贝数，和染色体 将设立地点。 AQP 6和其他新的部分cDNA 眼睛的遗传特征类似。 二.分布和表达研究。 细胞和亚细胞 AQP 1、4、5和6的位置将在正常情况下精确确定。 免疫组化和免疫电镜观察。 这些水通道蛋白的组成性表达将在小鼠眼内进行研究。 在胎儿发育期间以及对药理学和 荷尔蒙刺激 三.患者研究。 AQP 1基因敲除突变的患者将被 检查视力障碍 最近的病人样本 将对角膜移植合作研究进行检查， Colton血型抗原中的不相容性可能导致 移植排斥反应，因为这些是AQP 1内的蛋白质多态性 其在角膜中丰富。 水通道蛋白的免疫组化分布 将在病理标本的组织中评估1、4、5和6 包括角膜营养不良、开角型青光眼、视网膜 恶化和老化。 血清和淋巴细胞从患者 干燥综合征将检查免疫反应的证据， AQP5。

Movement of water across the plasma membrane is critical to the functions of several tissues in eye. Nevertheless, the molecular structures responsible for water transport were enigmatic until the recent discovery of CHIP (AQP1) and other members of the aquaporin family of membrane water channel proteins. Multiple aquaporins are being identified in eye: AQP1 is in nonpigmented ciliary epithelium, corneal endothelium, lens epithelium, and trabecular meshwork; AQP4 is in neurons; AQP5 is in corneal epithelium, lacrimal and salivary glands; AQP6 is in retinal pigmented epithelium. Analyses of these proteins may now provide molecular insight into water transport during normal vision and in several diseases of eye. I. Genetic studies. Human, murine, and bovine cDNAs for AQP5 will be isolated and compared for conservation of residues potentially important to function, The AQP5 gene(s) will be cloned from human and mouse genomic libraries, their organization, copy number, and chromosomal locations will be established. AQP6 and other novel partial cDNAs from eye will be genetically characterized similarly. II. Distribution and expression studies. The cellular and subcellular location of AQPs 1, 4, 5, and 6 will be precisely established in normal ocular tissues by immunohistochemistry and immunoelectronmicroscopy. Constitutive expression of these AQPs will be studied in murine ocular tissues during fetal development and in response to pharmacologic and hormonal stimuli. III. Patient studies. Patients with knockout mutations in AQP1 will be examined for visual disturbances. Patient samples from the recent Collaborative Corneal Transplant Study will be examined for incompatibles in the Colton blood group antigens which may contribute to graft rejection, since these are protein polymorphisms within AQP1 which is abundant in cornea. Immunohistochemical distributions of AQPs 1, 4, 5, and 6 will be assessed in tissues from pathological specimens including corneal dystrophies, open angle glaucomas, retinal deteriorations, and aging. Serum and lymphocytes from patients with Sjogren's syndrome will be examined for evidence of immune responses to AQP5.