C-reactive protein isoforms differentially affect outer blood-retinal barrier integrity and function
C-reactive protein isoforms differentially affect outer blood-retinal barrier integrity and function
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DOI：
10.1152/ajpcell.00057.2016
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发表时间：
2017-03-01
影响因子：
5.5
通讯作者：
Martorell, Jordi
中科院分区：
文献类型：
--
作者：
Molins, Blanca;Anna Pascual, Mendez;Martorell, Jordi
视网膜色素上皮（RPE）形成外部血-视网膜屏障（oBRB）并且是早期年龄相关性黄斑变性（AMD）的主要目标。C-反应蛋白（CRP）是慢性炎症和AMD的血清生物标志物，存在两种不同的同种型，单体（mCRP）和五聚体（pCRP），其可能对RPE中的炎症和屏障功能具有不同的影响。本研究报告的结果表明，mCRP而不是pCRP通过增加细胞旁通透性和破坏RPE细胞中的紧密连接蛋白ZO-1和occludin来损害RPE功能。此外，我们评估了临床环境中常用药物对mCRP诱导的屏障功能障碍的影响。我们发现皮质类固醇（甲泼尼龙）和抗VEGF药物（贝伐单抗）可预防mCRP诱导的ARPE-19屏障破坏和IL-8产生。此外，贝伐珠单抗还能够逆转mCRP刺激后mCRP诱导的IL-8升高。总之，视网膜组织中mCRP的存在可能导致oBRB的破坏，在皮质类固醇或抗VEGF药物的存在下，这种作用可能会改变。
The retinal pigment epithelium (RPE) forms the outer blood-retinal barrier (oBRB) and is the prime target of early age-related macular degeneration (AMD). C-reactive protein (CRP), a serum biomarker for chronic inflammation and AMD, presents two different isoforms, monomeric (mCRP) and pentameric (pCRP), that may have a different effect on inflammation and barrier function in the RPE. The results reported in this study suggest that mCRP but not pCRP impairs RPE functionality by increasing paracellular permeability and disrupting the tight junction proteins ZO-1 and occludin in RPE cells. Additionally, we evaluated the effect of drugs commonly used in clinical settings on mCRP-induced barrier dysfunction. We found that a corticosteroid (methylprednisolone) and an anti-VEGF agent (bevacizumab) prevented mCRP-induced ARPE-19 barrier disruption and IL-8 production. Furthermore, bevacizumab was also able to revert mCRP-induced IL-8 increase after mCRP stimulation. In conclusion, the presence of mCRP within retinal tissue may lead to disruption of the oBRB, an effect that may be modified in the presence of corticosteroids or anti-VEGF drugs.