Liu Xiao-Qiang, Kobayashi Hideyuki, Jin Zi-Bing, Wada Akihiko, Nao-I Nobuhis
Department of Ophthalmology, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki, Japan.
Mol Vis. 2007 Mar 1;13:309-17.
The inwardly rectifying potassium channel protein Kir4.1 and the water channel protein aquaporin-4 (AQP4) have been suggested to play essential roles in the potassium and water homeostasis of the retina. In this study, we investigated the expression of Kir4.1 and AQP4 in the retina during endotoxin-induced uveitis (EIU) in rats.
EIU was induced in male Wistar rats by intravitreal injection of lipopolysaccharide (LPS). The severity of the EIU was evaluated by clinical and histopathological examination. The expression of Kir4.1 and AQP4 in the retina was detected by semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR), Western blotting, and immunohistochemical staining.
In the animal model of EIU, the clinical changes correlated well with the histopathological findings. The inflammation peaked at 24 h and resolved by seven day. After an intravitreal LPS injection, the expression of Kir4.1 in the retina showed a significant decline at both the protein and mRNA levels. In the early stages of EIU, the expression of Kir4.1 mRNA decreased sharply, reaching a minimum at 12 h (31%, p<0.001). It then increased gradually and had partially recovered 14 days after LPS injection (92%, p>0.05). The expression of Kir4.1 protein decreased significantly, reaching a minimum at three days after the LPS injection (43%, p<0.001). Thereafter, it increased slightly but was maintained at a low level until 14 days after LPS injection (64%, p<0.001). In contrast, the expression of AQP4 mRNA remained almost unchanged after LPS treatment (p>0.05). The expression of AQP4 protein was only slightly reduced at one day (82%, p>0.05) after LPS injection and then increased gradually and had nearly recovered to the basal level at 14 days after LPS injection.
EIU differently alters the expression of Kir4.1 and AQP4 in the retina. The differential expression of Kir4.1 and AQP4 during EIU implies a disturbance of water and potassium transport in the retina, which may contribute to the retinal edema during ocular inflammation.
内向整流钾通道蛋白Kir4.1和水通道蛋白水通道蛋白4（AQP4）被认为在视网膜的钾和水平衡中起重要作用。在本研究中，我们调查了大鼠内毒素诱导性葡萄膜炎（EIU）期间视网膜中Kir4.1和AQP4的表达。
通过玻璃体内注射脂多糖（LPS）诱导雄性Wistar大鼠发生EIU。通过临床和组织病理学检查评估EIU的严重程度。通过半定量逆转录聚合酶链反应（RT-PCR）、蛋白质印迹和免疫组织化学染色检测视网膜中Kir4.1和AQP4的表达。
在EIU动物模型中，临床变化与组织病理学结果密切相关。炎症在24小时达到高峰，并在7天内消退。玻璃体内注射LPS后，视网膜中Kir4.1的表达在蛋白质和mRNA水平均显著下降。在EIU早期，Kir4.1 mRNA表达急剧下降，在12小时达到最低水平（31%，p<0.001）。然后逐渐增加，在LPS注射后14天部分恢复（92%，p>0.05）。Kir4.1蛋白表达显著下降，在LPS注射后3天达到最低水平（43%，p<0.001）。此后，略有增加，但在LPS注射后14天一直维持在低水平（64%，p<0.001）。相比之下，LPS处理后AQP4 mRNA表达几乎没有变化（p>0.05）。AQP4蛋白表达在LPS注射后1天仅略有降低（82%，p>0.05），然后逐渐增加，在LPS注射后14天几乎恢复到基础水平。
EIU对视网膜中Kir4.1和AQP4的表达有不同影响。EIU期间Kir4.1和AQP4的差异表达意味着视网膜中水和钾转运的紊乱，这可能导致眼部炎症期间的视网膜水肿。
