Protection of the cornea from UVB radiation by elevated potassium in tears
Protection of the cornea from UVB radiation by elevated potassium in tears
批准号:
8574193
负责人:
JOHN L UBELS
金额:
$37.59万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2013
资助国家:
美国
项目状态:
已结题
起止时间:
2013-09-30 至 2017-09-29
关键词:
Adverse effectsApoptosisApoptoticBathingCaspaseCell Culture TechniquesCellsCorneaDoseElectrolytesEpithelial CellsEpitheliumEquilibriumEventExposure toExtracellular FluidEyeEye diseasesFamily suidaeFilmGoalsHealthInvestigationLeadMaintenanceModelingPathway interactionsPatientsPhysiologicalPotassiumPotassium ChannelResearchRetinaRiskRoleSalineSignal PathwaySignal TransductionSkinSmall Interfering RNATestingTumor Necrosis Factor Ligand Superfamily Member 6UV Radiation ExposureUV inducedUVB inducedUltraviolet B RadiationUltraviolet RaysWorkcaspase-3caspase-8channel blockerscorneal epitheliumdesigneye drynessknock-downlensocular surfacepotassium ionpreventpublic health relevanceultravioletultraviolet damage
中文摘要
项目摘要
眼泪,在大多数情况下,有电解质成分像其他细胞外液。眼泪
然而,在其他实施方案中,K+浓度是独特的,因为K+浓度([K+]为约20-25 mM,相比之下,在其他实施方案中为约5 mM)是独特的。
细胞外液暴露于紫外线辐射引起细胞凋亡。UVB辐射剂量
与室外UVB暴露的环境水平相关的激活K+通道,导致细胞内
K+(K+i)。我们已经证明,角膜上皮细胞在暴露于25 mM K+的培养基中孵育,
UVB防止K+i损失并抑制凋亡机制的激活。这些观察结果支持了我们的
总的假设是,眼泪中高浓度的钾离子有助于保护
角膜上皮免受环境UVB诱导的损伤是通过减少细胞内K+通道时的损失
被UVB激活。我们现在建议研究UVB通过细胞内信号传导机制,
激活角膜上皮细胞中的K+通道和凋亡信号。
本研究的具体目的是:1)阐明Fas配体-
独立的,UVB诱导的细胞凋亡信号通路的激活和K+通道的激活。这将
通过研究UVB对角膜细胞凋亡途径和K+通道激活的影响,
在Fas和FADD的siRNA敲低或caspase-8的抑制之后,研究上皮细胞是否
UVB诱导的K+通道激活是细胞凋亡途径激活的主要事件。K+通道
角膜上皮细胞将使用PCR阵列鉴定。然后将使用siRNA敲除特异性的
渠道随后将研究UVB诱导的细胞凋亡激活,以及
当特定通道被敲除时,UVB对K+电流和细胞内[K+]的影响;
分离的猪眼模型,UVB对完整角膜上皮的影响将在配置中进行研究
其允许以模拟洗浴的方式用生理盐水灌注眼表面
眼角膜破裂将检验升高的[K+]将保护浅层角膜的假设
紫外线诱导的细胞凋亡的细胞层。
英文摘要
Project summary
The tears, for the most part, have an electrolyte composition like other extracellular fluids. The tears
are unique, however, in that the K+ concentration ([K+] is about 20-25 mM, compared to about 5 mM in other
extracellular fluids. Exposure to ultraviolet radiation causes apoptosis of cells. UVB radiation at doses
relevant to ambient levels of outdoor UVB exposure activates K+ channels leading to rapid loss of intracellular
K+ (K+i). We have shown that incubation of corneal epithelial cells in medium with 25 mM K+ after exposure to
UVB prevents loss of K+i and inhibits activation of apoptotic mechanisms. These observations support our
overall hypothesis that the high concentration of potassium ions in tears contributes to the protection of the
corneal epithelium from ambient UVB-induced damage by reducing the loss of intracellular K+ when channels
are activated by UVB. We now propose to investigate the intracellular signaling mechanisms by which UVB
activates K+ channels and apoptotic signaling in corneal epithelial cells.
The specific aims of the proposed research are: 1) to elucidate the relationships between Fas ligand-
independent, UVB-induced activation of apoptotic signaling pathways and activation of K+ channels. This will
be accomplished by studying the effects of UVB on apoptotic pathways and K+ channel activation in corneal
epithelial cells after siRNA knockdown of Fas and FADD, or inhibition of caspase-8; 2) To investigate whether
UVB-induced K+ channel activation is the primary event in activation of apoptotic pathways. K+ channels in
corneal epithelial cells will be identified using a PCR array. siRNA will then be used to knock down specific
channels. This will be followed by investigation of UVB-induced activation of apoptosis, as well as effects of
UVB on K+ currents and intracellular [K+] when specific channels have been knocked down; 3) Using an
isolated pig eye model, effects of UVB on the intact corneal epithelium will be investigated in a configuration
that allows for superfusion of the ocular surface with physiologic saline in a manner that models the bathing
of the cornea with tears. The hypothesis will be tested that elevated [K+] will protect the superficial corneal
cell layers from UV-induced apoptosis.
期刊论文(4)
专著(0)
科研奖励(0)
会议论文
DOI:
10.1016/j.jtos.2016.05.001
发表时间:
2016-07
期刊:
The ocular surface
影响因子:
--
作者:
[Glupker CD, Boersma PM, Schotanus MP, Haarsma LD, Ubels JL]
通讯作者:
Ubels JL
DOI:
10.1016/j.exer.2015.11.003
发表时间:
2016-04
期刊:
Experimental eye research
影响因子:
3.4
作者:
[Ubels JL, Glupker CD, Schotanus MP, Haarsma LD]
通讯作者:
Haarsma LD
DOI:
10.1016/j.exer.2016.07.014
发表时间:
2016-10
期刊:
EXPERIMENTAL EYE RESEARCH
影响因子:
3.4
作者:
[Leerar, John R., Glupker, Courtney D., Schotanus, Mark P., Ubels, John L.]
通讯作者:
Ubels, John L.
Elevated potassium ion in lacrimal fluid and the health of the ocular surface
-
批准号:7237639
-
项目类别:
-
资助金额:$18.72万
-
财政年份:2007
-
负责人:JOHN L UBELS
-
依托单位:
Elevated potassium ion in lacrimal fluid and the health of the ocular surface
-
批准号:7384420
-
项目类别:
-
资助金额:$18.44万
-
财政年份:2007
-
负责人:JOHN L UBELS
-
依托单位:
Elevated potassium ion in lacrimal fluid and the health of the ocular surface
-
批准号:7627247
-
项目类别:
-
资助金额:$18.91万
-
财政年份:2007
-
负责人:JOHN L UBELS
-
依托单位:
Elevated potassium ion in lacrimal fluid and the health of the ocular surface
-
批准号:7847247
-
项目类别:
-
资助金额:$0.82万
-
财政年份:2007
-
负责人:JOHN L UBELS
-
依托单位:
Analysis of Lacrimal Gland by Laser Microdissection
-
批准号:6644709
-
项目类别:
-
资助金额:$5.63万
-
财政年份:2003
-
负责人:JOHN L UBELS
-
依托单位:
RETINOIDS AND LACRIMAL GLAND FUNCTION
-
批准号:2159507
-
项目类别:
-
资助金额:$18.94万
-
财政年份:1991
-
负责人:JOHN L UBELS
-
依托单位:
THE TEAR FILM AND THE OCULAR SURFACE: VITAMIN A IN TEAR
-
批准号:3260921
-
项目类别:
-
资助金额:$15.94万
-
财政年份:1991
-
负责人:JOHN L UBELS
-
依托单位:
THE TEAR FILM AND THE OCULAR SURFACE: VITAMIN A IN TEARS
-
批准号:3260922
-
项目类别:
-
资助金额:$13.95万
-
财政年份:1991
-
负责人:JOHN L UBELS
-
依托单位:
RETINOIDS AND LACRIMAL GLAND FUNCTION
-
批准号:2159509
-
项目类别:
-
资助金额:$6.03万
-
财政年份:1991
-
负责人:JOHN L UBELS
-
依托单位:
RETINOIDS AND LACRIMAL GLAND FUNCTION
-
批准号:2019499
-
项目类别:
-
资助金额:$15.0万
-
财政年份:1991
-
负责人:JOHN L UBELS
-
依托单位:
THE ROLE OF RETINOIDS IN LACRIMAL GLAND FUNCTION
-
批准号:6131750
-
项目类别:
-
资助金额:$15.91万
-
财政年份:1991
-
负责人:JOHN L UBELS
-
依托单位:
RETINOIDS AND LACRIMAL GLAND FUNCTION
-
批准号:2608580
-
项目类别:
-
资助金额:$15.6万
-
财政年份:1991
-
负责人:JOHN L UBELS
-
依托单位:
RETINOIDS AND LACRIMAL GLAND FUNCTION
-
批准号:2159510
-
项目类别:
-
资助金额:$15.69万
-
财政年份:1991
-
负责人:JOHN L UBELS
-
依托单位:
TEAR FILM AND THE OCULAR SURFACE--VITAMIN A IN TEARS
-
批准号:3260920
-
项目类别:
-
资助金额:$14.88万
-
财政年份:1991
-
负责人:JOHN L UBELS
-
依托单位:
THE ROLE OF RETINOIDS IN LACRIMAL GLAND FUNCTION
-
批准号:6384486
-
项目类别:
-
资助金额:$15.96万
-
财政年份:1991
-
负责人:JOHN L UBELS
-
依托单位:
THE ROLE OF RETINOIDS IN LACRIMAL GLAND FUNCTION
-
批准号:6518341
-
项目类别:
-
资助金额:$16.03万
-
财政年份:1991
-
负责人:JOHN L UBELS
-
依托单位:
RETINOIDS AND LACRIMAL GLAND FUNCTION
-
批准号:2159508
-
项目类别:
-
资助金额:$11.63万
-
财政年份:1991
-
负责人:JOHN L UBELS
-
依托单位:
THE TEAR FILM AND THE OCULAR SURFACE: VITAMIN A IN TEAR
-
批准号:3260913
-
项目类别:
-
资助金额:$11.12万
-
财政年份:1985
-
负责人:JOHN L UBELS
-
依托单位:
TEAR FILM AND THE OCULAR SURFACE: VITAMIN A IN TEAR
-
批准号:3260915
-
项目类别:
-
资助金额:$1.9万
-
财政年份:1985
-
负责人:JOHN L UBELS
-
依托单位:
THE TEAR FILM AND THE OCULAR SURFACE: VITAMIN A IN TEAR
-
批准号:3260916
-
项目类别:
-
资助金额:$10.3万
-
财政年份:1985
-
负责人:JOHN L UBELS
-
依托单位:
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