Blood-retinal barrier disruption and ultrastructural changes in the hypoxic retina in adult rats: the beneficial effect of melatonin administration
Blood-retinal barrier disruption and ultrastructural changes in the hypoxic retina in adult rats: the beneficial effect of melatonin administration
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DOI：
10.1002/path.2195
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发表时间：
2007-08-01
影响因子：
7.3
通讯作者：
Ling, E. A.
中科院分区：
文献类型：
--
作者：
Kaur, C.;Sivakumar, V.;Ling, E. A.
本文观察了成年大鼠视网膜星形胶质细胞和苗勒细胞在缺氧后的反应性变化。沿着，使用荧光和电子致密示踪剂评估血视网膜屏障（BRB）的完整性。在缺氧大鼠，胶质细胞酸性蛋白（GFAP）和水通道蛋白-4（AQ 4）的mRNA和蛋白表达显著增加。免疫荧光双标法鉴定AQ 4阳性细胞为星形胶质细胞和Muller细胞。与对照组相比，缺氧视网膜的另一个变化是褪黑激素含量显着减少。在这方面，外源性褪黑激素的管理减少了血管内皮生长因子（VEGF）和一氧化氮（NO）的组织浓度，两者都在缺氧大鼠升高。缺氧视网膜的一个主要结构变化是星形胶质细胞和Muller细胞突起肿胀，但这在褪黑激素给药后明显减弱。腹膜内或静脉内注射异硫氰酸罗丹明（RhIC）或辣根过氧化物酶（HRP）后，在缺氧大鼠的视网膜中观察到两种示踪剂的渗漏，但在对照组中没有观察到，这表明BRB的功能完整性在缺氧/复氧中受到损害。这表明，在缺氧视网膜中VEGF和NO产生的组织浓度的增加有助于视网膜血管的通透性增加。缺氧时星形胶质细胞和Muller细胞中水转运蛋白AQ 4的同时上调表明其参与水肿形成。由于褪黑激素有效地降低了缺氧大鼠视网膜的血管通透性，证明了减少泄漏的RhIC，我们建议，它的管理可能是潜在的好处与视网膜缺氧相关的视网膜水肿的管理。版权所有（C）2007大不列颠和爱尔兰病理学会。出版社：John Wiley & Sons，Ltd
Reactive changes in astrocytes and Muller cells in the retina of adult rats subjected to hypoxia were investigated. Along with this, the integrity of the blood-retinal barrier (BRB) was assessed using fluorescent and electron-dense tracers. In hypoxic rats, mRNA and protein expression of glial fibrillary acidic protein (GFAP) and aquaporin-4 (AQ4) were significantly increased. AQ4 inummoreactive cells were identified as astrocytes and Muller cells by double immunofluorescence labelling. Another alteration in the hypoxic retina was marked reduction in melatonin content compared to controls. In this connection, administration of exogenous melatonin reduced the tissue concentration of vascular endothelial growth factor (VEGF) and nitric oxide (NO); both were elevated in hypoxic rats. A major structural change in the hypoxic retina was swelling of astrocyte and Muller cell processes but this was noticeably attenuated after melatonin administration. Following an intraperitoneal or intravenous injection of rhodamine isothiocyanate (RhIC) or horseradish peroxidase (HRP), leakage of both tracers was observed in the retina in hypoxic rats but not in the controls, indicating that the functional integrity of the BRB is compromised in hypoxia/reoxygenation. It is suggested that enhanced tissue concentration of VEGF and NO production in the hypoxic retina contribute to increased permeability of the retinal blood vessels. The concurrent up-regulation of AQ4, a water-transporting protein, in astrocytes and Muller cells in hypoxia suggests its involvement in oedema formation. Since melatonin effectively reduced the vascular permeability in the retina of hypoxic rats, as evidenced by reduced leakage of RhIC, we suggest that its administration may be of potential benefit in the management of retinal oedema associated with retinal hypoxia. Copyright (C) 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.