Elevated potassium ion in lacrimal fluid and the health of the ocular surface

泪液中钾离子升高与眼表健康

• 批准号: 7847247
• 负责人: JOHN L UBELS
• 金额: $ 0.82万
• 依托单位: CALVIN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-06-01 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7847247
• 关键词: Address; Affect; Apoptotic; Biology; Carrier Proteins; Cell Line; Cell Survival; Cell Volumes; Cell membrane; Cells; Confocal Microscopy; Cornea; Culture Media; Development; Disease; Dose; Duct (organ) structure; Electrolytes; Environment; Epithelial; Epithelial Cells; Exposure to; Extracellular Fluid; Eye; Eye diseases; Film; Genes; Goals; Health; Immunofluorescence Immunologic; Individual; Ion Channel; Ions; Lacrimal gland structure; Liquid substance; Lymphocyte; Maintenance; Measurement; Measures; Membrane Potentials; Pathway interactions; Patients; Potassium; Potassium Channel; Process; Rattus; Regulation; Research; Research Personnel; Rest; Retina; Role; Signal Transduction; System; Techniques; Ultraviolet Rays; Work; apoptosis in lymphocytes; base; corneal epithelium; extracellular; eye dryness; improved; lacrimal; lens; ocular surface; patch clamp; potassium ion; prevent; programs; ultraviolet

DESCRIPTION (provided by applicant): The tears differ from most extracellular fluids in that the K+ concentration of tears is about 20 mEq/l. It is thought that the ducts of the lacrimal gland secrete K+; however, the mechanism of this secretion has not been fully elucidated, and the purpose of the high [K+] in tears with respect to its relationship to the cells of the ocular surface is unknown. The key hypotheses to be addressed are based on these observations: 1) Lacrimal gland ducts express K+ transporters and channels consistent with secretion of K+ by the ducts, 2) UV radiation causes opening of K+ channels and loss of K+ from corneal epithelial cells and this loss of K+ activates apoptotic pathways. 3) Elevating extracellular K+ ([K+]o) prevents activation of apoptotic pathways in lymphocytes. We propose that the lacrimal gland duct cells secrete fluid high in K+, which provides the ocular surface with an extracellular ionic environment that protects these cells from the deleterious effects of ambient levels of ultraviolet (UV) radiation. The relatively high level of K+ in tears prevents the loss of intracellular K+ and the activation of apoptotic mechanisms when ocular surface cells are exposed to UV radiation. The specific aims of the proposed research are, 1) to determine, using patch clamp recording, whether K+ and Cl- channels, previously identified in lacrimal duct cells by microarrays and confocal microscopy are active in these cells. 2) To determine the role of elevated [K+] in tears, corneal epithelial cells will be exposed to UV radiation in the presence of varying [K+]o followed by measurement of cell viability, activation of apoptotic pathways and activity of ion channels, 3) To determine whether elevating [K+] in culture medium will promote the proliferation and viability corneal epithelial cells in culture. This study of the role of high potassium in tears will elucidate the relationship of the tears to the health of the eye in normal individuals and dry-eye patients. Everyone is exposed to ambient UV radiation and the proposed research will help to explain how the cornea protects the lens and retina from UV radiation while suffering minimal damage. In dry eye disease an inadequate tear film may make the cornea more susceptible to damage by UV radiation, thereby contributing to the disease process. If the high potassium in tears is important for the health of the ocular surface, this information will be useful in the development of improved treatments for dry eye disease.

描述（由申请人提供）：眼泪与大多数细胞外流体有所不同，因为K+的泪液浓度约为20 meq/l。据认为，泪腺的管道分泌K+。然而，这种分泌的机制尚未完全阐明，并且在其与眼表面细胞的关系中，高[K+]的目的是未知的。要解决的关键假设基于以下观察结果：1）泪腺导管表达K+转运蛋白和与K+分泌的通道，与管道分泌一致，2）紫外线辐射引起K+通道的打开以及Corneal上皮细胞的K+损失K+的损失，以及K+ Actip Actip Actip Actias Actip Acties Acties Acties Acties Acties Acties Acties Acties Actications Apptotic Pachotic Pathrowe。 3）升高细胞外K+（[K+] O）可防止淋巴细胞中凋亡途径的激活。我们提出，泪腺管细胞分泌K+中的流体，该液为眼部表面提供了细胞外离子环境，可保护这些细胞免受环境水平紫外线（UV）辐射的有害影响。当眼表面细胞暴露于紫外线辐射时，相对较高的K+流泪中的K+阻止细胞内K+的丧失和凋亡机制的激活。拟议的研究的具体目的是，1）使用贴片夹记录，是否在这些细胞中通过微阵列和共聚焦显微镜在泪管细胞中鉴定出的K+和Cl-通道是否活跃。 2）为了确定[K+]在泪液中的作用，角膜上皮细胞将在存在不同的[K+] O之后暴露于紫外线辐射，然后测量细胞活力的测量，凋亡途径的激活和离子通道的活性，3），3）在培养基中升高[K+]是否会在培养基中升高[K+]是否会在培养基中促进细胞的培养细胞和细胞的培养。这项关于高钾在泪水中的作用的研究将阐明正常个体和干眼患者的眼泪与眼睛健康的关系。每个人都暴露于环境紫外线辐射，拟议的研究将有助于解释角膜如何保护镜头和视网膜免受紫外线辐射的影响，同时遭受最小的损害。在干眼症中，撕裂膜不足可能会使角膜更容易受到紫外线辐射的损害，从而导致疾病过程。如果泪水中的高钾对于眼表面的健康很重要，则此信息将有助于改善干眼症治疗的治疗方法。

项目成果

Inhibition of UV-B induced apoptosis in corneal epithelial cells by potassium channel modulators.

钾通道调节剂抑制 UV-B 诱导的角膜上皮细胞凋亡。

• DOI: 10.1016/j.exer.2009.10.005
• 发表时间: 2010
• 期刊: Experimental eye research
• 影响因子: 3.4
• 作者: Ubels,JohnL;Schotanus,MarkP;Bardolph,SusanL;Haarsma,LorenD;Koetje,LeahR;Louters,JulienneR
• 通讯作者: Louters,JulienneR

Differential regulation of GLUT1 activity in human corneal limbal epithelial cells and fibroblasts.

• DOI: 10.1016/j.biochi.2012.09.022
• 发表时间: 2013-02
• 期刊: BIOCHIMIE
• 影响因子: 3.9
• 作者: Kuipers, David P.;Scripture, Jared P.;Gunnink, Stephen M.;Salie, Matthew J.;Schotanus, Mark P.;Ubels, John L.;Louters, Larry L.
• 通讯作者: Louters, Larry L.