Wolfensberger T J, Dmitriev A V, Govardovskii V I
Hôpital Ophtalmique Jules Gonin, University of Lausanne, Switzerland.
Doc Ophthalmol. 1999;97(3-4):261-71. doi: 10.1023/a:1002496223131.
The lipophilic carbonic anhydrase (CA) inhibitor acetazolamide has been shown to enhance subretinal fluid resorption, reduce subretinal pH, and can improve cystoid macular edema, but its clinical use is limited by systemic side effects. While these are most likely a result of inhibiting intracellular CA isoenzymes, retinal pigment epithelial (RPE) transport is thought to be modulated via membrane-bound CA. This study investigates whether benzolamide, a hydrophilic CA inhibitor that does not readily penetrate cell membranes, is sufficient to modulate subretinal volume and pH.
Volume and pH were assessed in the subretinal space (SRS) of the perfused chick retina-RPE-choroid preparation by calculating these variables from data obtained with two different double-barreled, ion-selective electrodes (H+ for pH and the extracellular space marker tetramethylammonium (TMA+) for SRS volume). Light induced variations and changes in baseline measurements were recorded before and after addition of 10(-4) M acetazolamide or benzolamide to the basal perfusion.
Basal perfusion with either drug induced both an acidification of the SRS by 0.02-0.04 pH units, which occurred within 60 s, as well as an increase in the amplitude of the light-induced alkalinisation of the SRS. TMA+ concentration in the SRS increased steadily over a period of several minutes after basal perfusion with either of the CA inhibitors, and the calculated SRS volume was reduced by 40% within 8-10 min.
The observation that benzolamide had effects equal to acetazolamide suggests that inhibition of membrane-bound CA at the basolateral membrane of the RPE is sufficient to decrease subretinal pH and volume. This may represent a clinically important mechanism for the resorption of sub- and intraretinal fluid.
亲脂性碳酸酐酶（CA）抑制剂乙酰唑胺已被证明可增强视网膜下液吸收、降低视网膜下pH值，并可改善黄斑囊样水肿，但其临床应用受到全身副作用的限制。虽然这些副作用很可能是抑制细胞内CA同工酶的结果，但视网膜色素上皮（RPE）转运被认为是通过膜结合CA进行调节的。本研究调查亲水性CA抑制剂苯唑酰胺（不易穿透细胞膜）是否足以调节视网膜下体积和pH值。
通过从两种不同的双管离子选择性电极（用于pH值的H+和用于视网膜下间隙体积的细胞外空间标记物四甲基铵（TMA+））获得的数据计算这些变量，在灌注的鸡视网膜-RPE-脉络膜制剂的视网膜下间隙（SRS）中评估体积和pH值。在基础灌注中添加10（-4）M乙酰唑胺或苯唑酰胺之前和之后，记录光诱导的变化和基线测量的变化。
用任何一种药物进行基础灌注均导致SRS酸化0.02 - 0.04个pH单位，这在60秒内发生，同时光诱导的SRS碱化幅度增加。在用任何一种CA抑制剂进行基础灌注后的几分钟内，SRS中的TMA+浓度稳步增加，并且计算出的SRS体积在8 - 10分钟内减少了40%。
苯唑酰胺与乙酰唑胺效果相同的观察结果表明，抑制RPE基底外侧膜上的膜结合CA足以降低视网膜下pH值和体积。这可能代表视网膜下和视网膜内液吸收的一个临床重要机制。
