Choroidal Mast Cells in Retinal Pathology A Potential Target for Intervention
Choroidal Mast Cells in Retinal Pathology A Potential Target for Intervention
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DOI：
10.1016/j.ajpath.2015.04.002
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发表时间：
2015-08-01
影响因子：
6
通讯作者：
de Kozak, Yvonne
中科院分区：
文献类型：
--
作者：
Bousquet, Elodie;Zhao, Min;de Kozak, Yvonne
肥大细胞在眼部炎症的发生中起重要作用，但肥大细胞脱颗粒对眼部病理的影响尚不明确。我们通过结膜下局部注射化合物48/80诱导肥大细胞脱颗粒。注射后15分钟，脉络膜可见肥大细胞脱颗粒，注射后3小时，肥大细胞脱颗粒增多。眼前节炎症的临床征象与肥大细胞脱颗粒相平行。用光学相干断层扫描观察脉络膜血管扩张和浆液性视网膜脱离，并经组织学证实。结膜下注射色甘酸二钠可显著降低SRDS的发生率，表明肥大细胞脱颗粒参与了后段病变。中性粒细胞和巨噬细胞的浸润与眼中膜肿瘤坏死因子-a、CXCL1、IL-6、IL-5、趋化因子配体2和IL-1β浓度的升高有关。对血管内皮生长因子和IL-18含量的分析表明，与IL-18浓度相比，血管内皮生长因子的进化是相反的，这表明它们相互调节着彼此的产生。这些结果表明，眼肥大细胞的局部脱颗粒引起了急性眼部炎症、扩张、脉络膜血管通透性增加和SRDS。肥大细胞在视网膜疾病中的作用有待进一步研究。药物抑制肥大细胞脱颗粒可能是一个潜在的干预靶点。
Mast cells are important in the initiation of ocular inflammation, but the consequences of mast cell degranulation on ocular pathology remain uncharacterized. We induced mast cell degranulation by local subconjunctival injection of compound 48/80. Initial degranulation of mast cells was observed in the choroid 15 minutes after the injection and increased up to 3 hours after injection. Clinical signs of anterior segment inflammation paralleled mast cell degranulation. With the use of optical coherence tomography, dilation of choroidal vessels and serous retinal detachments (SRDs) were observed and confirmed by histology. Subconjunctival injection of disodium cromoglycate significantly reduced the rate of SRDs, demonstrating the involvement of mast cell degranulation in posterior segment disorders. The infiltration of polymorphonuclear and macrophage cells was associated with increased ocular media concentrations of tumor necrosis factor-a, CXCL1, IL-6, IL-5, chemokine ligand 2, and IL-1 beta. Analysis of the amounts of vascular endothelial growth factor and IL-18 showed an opposite evolution of vascular endothelial growth factor compared with IL-18 concentrations, suggesting that they regulate each other's production. These findings suggest that the local degranulation of ocular mast cells provoked acute ocular inflammation, dilation, increased vascular permeability of choroidal vessels, and SRDs. The involvement of mast cells in retinal diseases should be further investigated. The pharmacologic inhibition of mast cell degranulation may be a potential target for intervention.