AQUAPORIN WATER CHANNEL PROTEINS IN EYE

点击翻译按钮获取中文摘要

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.