AQUAPORIN WATER CHANNEL PROTEINS IN EYE

水在质膜上的运动对 眼部几种组织的功能。然而，分子 负责水运输的结构一直是谜一样的，直到 ChIP(AQP1)等水通道蛋白的最新发现 膜水通道蛋白家族。多个水通道蛋白 在眼睛中被识别：AQP1位于无色素的睫状上皮中， 角膜内皮、晶状体上皮和小梁网；AQP4是 AQP5表达于角膜上皮、泪腺和唾液腺； AQP6位于视网膜色素上皮中。对这些蛋白质的分析可能 现在提供正常视野下水运输的分子洞察力 以及几种眼科疾病。 一、基因研究。AQP5的人、小鼠和牛的cDNA将是 分离和比较潜在重要的残基的保守性 为了发挥作用，将从人和小鼠中克隆AQP5基因(S) 基因组文库、它们的组织、拷贝数和染色体 将建立地点。AQP6和其他新的来自 眼睛也会有类似的基因特征。 II.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建立 眼组织进行免疫组织化学和免疫电镜观察。 这些水通道蛋白的结构性表达将在小鼠眼部进行研究 胎儿发育过程中的组织以及对药物和 荷尔蒙刺激。 三、患者研究。AQP1基因敲除突变的患者将是 检查是否有视觉障碍。最近的病人样本 将检查协作性角膜移植研究 科尔顿血型抗原中的不相容可能有助于 对移植排斥反应，因为这些都是AQP1内的蛋白质多态性 它在角膜中含量丰富。水通道蛋白的免疫组织化学分布 1、4、5和6将在病理标本的组织中进行评估 包括角膜营养不良、开角型青光眼、视网膜 恶化和老化。慢性支气管炎患者的血清和淋巴细胞 将检查干燥综合征以寻找免疫反应的证据 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.