Transthyretin synthesis in rabbit ciliary pigment epithelium

Transthyretin synthesis in rabbit ciliary pigment epithelium
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DOI:
10.1016/j.exer.2005.02.003
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发表时间:
2005-09-01
影响因子:
3.4
通讯作者:
Tanihara, H
Tanihara, H
中科院分区:
医学3区
文献类型:
--
作者:
Kawaji, T;Ando, Y;Tanihara, H

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甲状腺素运载蛋白(TTR)相关的家族性淀粉样多发性神经病(FAP)的眼部症状表明,睫状色素上皮(CPE)可能合成TTR,其TTR可能导致淀粉样蛋白形成,除了来自血管和视网膜色素上皮(RPE)的TTR。为了明确眼组织中TTR合成的位点,我们进行了原位杂交和逆转录-聚合酶链反应(RT-PCR)定性检测TTR mRNA。此外,我们通过实时定量RT-PCR定量TTR mRNA的表达水平。此外,虽然TTR在血清水平上是抗急性期蛋白,但没有关于急性炎症期间眼组织中TTR表达变化的报道。为了研究炎症过程中眼组织TTR表达的变化,我们通过内毒素攻击诱导兔葡萄膜炎,并使用实时定量RT-PCR检测眼组织TTR mRNA表达的变化。原位杂交和RT-PCR定性显示,TTR mRNA不仅在RPE中,而且在CPE中。实时荧光定量RT-PCR结果显示,CPE中TTR mRNA的表达量约为RPE中TTR mRNA表达量的1/3。眼组织TTR mRNA表达随炎症程度的加重而降低。这些结果表明,在CPE中合成的TTR可能导致眼部表现,特别是青光眼,在FAR中TTR mRNA也作为眼组织中的抗急性期反应物。(c)2005爱思唯尔有限公司保留所有权利。
Ocular symptoms of transthyretin (TTR)-related familial amyloidotic polyneuropathy (FAP) suggest that ciliary pigment epithelium (CPE) may synthesize TTR and its TTR may lead to amyloid formation in addition to TTR from vessels and retinal pigment epithelium (RPE). To clarify sites of TTR synthesis in ocular tissues, we performed in situ hybridization and reverse transcription-polymerase chain reaction (RT-PCR) for qualitative detection of TTR mRNA. In addition, we quantified levels of TTR mRNA expression by means of real-time quantitative RT-PCR. Furthermore, although TTR is an anti-acute phase protein in serum level, no reports on changes in TTR expression in ocular tissues during acute inflammation exist. To investigate changes in TTR expression in ocular tissues during inflammation, we induced uveitis by endotoxin challenge in rabbits and used real-time quantitative RT-PCR to examine changes in TTR mRNA expression in ocular tissues. In situ hybridization and RT-PCR qualitatively demonstrated TTR mRNA not only in RPE but also in CPE. Real-time quantitative RT-PCR showed that the level of TTR mRNA expression in the CPE was about one-third of that in the RPE. TTR mRNA expression in ocular tissues decreased as the degree of inflammation increased. These results suggest that TTR synthesized in the CPE may lead to ocular manifestations, especially glaucoma, in FAR TTR mRNA also acts as an anti-acute phase reactant in ocular tissues. (c) 2005 Elsevier Ltd. All rights reserved.