IFNγ regulates retinal pigment epithelial fluid transport
IFNγ regulates retinal pigment epithelial fluid transport
复制标题
DOI：
10.1152/ajpcell.00255.2009
复制
发表时间：
2009-12-01
影响因子：
5.5
通讯作者：
Miller, Sheldon S.
中科院分区：
文献类型：
--
作者：
Li, Rong;Maminishkis, Arvydas;Miller, Sheldon S.
Li R，Maminishkis A，Banzon T，Wan Q，Jakirkee S，Chen S，米勒SS. IFN γ调节视网膜色素上皮细胞液体转运。美国生理学杂志细胞生理学297：C1452-C1465，2009年。首次发表于2009年9月30日; doi：10.1152/ajpcell.00255.2009。目前的实验表明，IFN γ受体主要定位于人视网膜色素上皮（RPE）的基底外侧膜。这些受体在人胎儿RPE的原代培养物中的活化抑制细胞增殖和迁移，降低RPE线粒体膜电位，改变跨上皮电位和电阻，并显著增加跨上皮液体吸收。这些作用通过JAK-STAT和p38 MAPK信号通路介导。第二信使信号通过cAMP-PKA途径和干扰素调节因子-1依赖的一氧化氮/cGMP的产生刺激了基底外侧膜的CFTR，并增加了经上皮液体吸收。使用视网膜再附着的大鼠模型的体内实验表明，施加到眼睛的前表面的IFN γ可以去除沉积在视网膜光感受器和RPE之间的细胞外或视网膜下空间中的额外流体。通过将PKA和JAK-STAT通路抑制剂的组合注射到视网膜下腔中来阻断这种额外液体的去除。这些结果证明了IFN γ在炎症性疾病过程中调节视网膜水化穿过外血-视网膜屏障的保护作用，并为可能的治疗干预提供了基础。
Li R, Maminishkis A, Banzon T, Wan Q, Jalickee S, Chen S, Miller SS. IFN gamma regulates retinal pigment epithelial fluid transport. Am J Physiol Cell Physiol 297: C1452-C1465, 2009. First published September 30, 2009; doi:10.1152/ajpcell.00255.2009.-The present experiments show that IFN gamma receptors are mainly localized to the basolateral membrane of human retinal pigment epithelium (RPE). Activation of these receptors in primary cultures of human fetal RPE inhibited cell proliferation and migration, decreased RPE mitochondrial membrane potential, altered transepithelial potential and resistance, and significantly increased transepithelial fluid absorption. These effects are mediated through JAK-STAT and p38 MAPK signaling pathways. Second messenger signaling through cAMP-PKA pathway- and interferon regulatory factor-1-dependent production of nitric oxide/cGMP stimulated the CFTR at the basolateral membrane and increased transepithelial fluid absorption. In vivo experiments using a rat model of retinal reattachment showed that IFN gamma applied to the anterior surface of the eye can remove extra fluid deposited in the extracellular or subretinal space between the retinal photoreceptors and RPE. Removal of this extra fluid was blocked by a combination of PKA and JAK-STAT pathway inhibitors injected into the subretinal space. These results demonstrate a protective role for IFN gamma in regulating retinal hydration across the outer blood-retinal barrier in inflammatory disease processes and provide the basis for possible therapeutic interventions.