Edelhauser H F, Geroski D H, Woods W D, Holley G P, Laniado-Schwartzman M
Department of Ophthalmology, Emory University School of Medicine, Atlanta, Georgia.
Invest Ophthalmol Vis Sci. 1993 Sep;34(10):2953-61.
To evaluate the effect of 12(R)hydroxyeicosatetraenoic acid (12(R)HETE) on corneal swelling when directly perfused to human and rabbit corneal endothelium.
Excised rabbit and human corneas were mounted in the in vitro specular microscope and the endothelium was perfused with 12(R)HETE at 10(-5), 10(-6), and 10(-7) mol/l. Both 12(R)HETE and 12(S)HETE were compared at equal molar (10(-6) mol/l) concentrations. The reversal of 12(R)HETE and ouabain corneal swelling was also compared. Endothelial permeability to carboxyfluorescein was measured after 12(R)HETE perfusion. High-performance liquid chromatographic analysis confirmed that 12(R)HETE remained in the perfusion media.
12(R)HETE caused a dose-dependent corneal swelling of 25 +/- 2, 24 +/- 1, and 14 +/- 0.5 microns/hr at 10(-5), 10(-6), and 10(-7) mol/l, respectively. Equal molar concentrations (10(-6) mol/l) of 12(S)HETE did not cause corneal swelling. Removal of the 12(R)HETE from the perfusion media resulted in reversal of corneal swelling whereas corneal swelling induced by ouabain did not reverse after ouabain removal. 12(R)HETE (10(-6) mol/l) perfused to the human corneal endothelium inhibited temperature reversal corneal thinning when compared to the paired corneal endothelium perfused with BSS Plus (Alcon Laboratories, Inc., Fort Worth, TX). Na/K adenosine triphosphatase activity was inhibited by 10(-6) mol/l ouabain by 35%, 10(-6) mol/l 12(R)HETE by 54%, and 10(-6) mol/l 12(S)HETE by 0.5%. Endothelial permeability to carboxyfluorescein was unaffected by 12(R)HETE.
12(R)HETE causes corneal swelling by inhibiting endothelial pump function. This inhibition of transport appears to be at least partly mediated by inhibition of endothelial Na/K adenosine triphosphatase.
评估12（R）-羟基二十碳四烯酸（12（R）-HETE）直接灌注人及兔角膜内皮时对角膜肿胀的影响。
将切除的兔角膜和人角膜安装在体外镜面显微镜上，用10^(-5)、10^(-6)和10^(-7)mol/L的12（R）-HETE灌注内皮。在等摩尔浓度（10^(-6)mol/L）下比较12（R）-HETE和12（S）-HETE。还比较了12（R）-HETE和哇巴因引起的角膜肿胀的逆转情况。在12（R）-HETE灌注后测量内皮对羧基荧光素的通透性。高效液相色谱分析证实12（R）-HETE保留在灌注介质中。
12（R）-HETE分别在10^(-5)、10^(-6)和10^(-7)mol/L时引起剂量依赖性角膜肿胀，速率分别为25±2、24±1和14±0.5微米/小时。等摩尔浓度（10^(-6)mol/L）的12（S）-HETE未引起角膜肿胀。从灌注介质中去除12（R）-HETE导致角膜肿胀逆转，而哇巴因引起的角膜肿胀在去除哇巴因后未逆转。与用BSS Plus（爱尔康实验室公司，得克萨斯州沃思堡）灌注的配对角膜内皮相比，灌注到人类角膜内皮的12（R）-HETE（10^(-6)mol/L）抑制了温度逆转角膜变薄。10^(-6)mol/L的哇巴因抑制钠钾三磷酸腺苷活性35%，10^(-6)mol/L的12（R）-HETE抑制54%，10^(-6)mol/L的12（S）-HETE抑制0.5%。12（R）-HETE不影响内皮对羧基荧光素的通透性。
12（R）-HETE通过抑制内皮泵功能引起角膜肿胀。这种对转运的抑制似乎至少部分是由内皮钠钾三磷酸腺苷的抑制介导的。
