Ruiz-Ederra Javier, Verkman A S
Department of Medicine and Physiology, Cardiovascular Research Institute, University of California, San Francisco, California 94143-0521, USA.
Invest Ophthalmol Vis Sci. 2007 Oct;48(10):4802-10. doi: 10.1167/iovs.07-0537.
Aquaporin-1 (AQP1) water channels are expressed widely in organ and tumor microvascular endothelia. Rapid microvessel proliferation occurs in growing tumors, diabetic and other retinopathies, and prenatal development. The purpose of this study was to investigate the role of AQP1 in retinal vessel proliferation.
Comparative studies were performed on wild-type compared with AQP1 null mice using an established mouse model of oxygen-induced retinopathy. Neonatal mice were maintained in a 75% oxygen atmosphere for 5 days to suppress angiogenesis and then were returned to room air to induce vessel proliferation. AQP1 expression was also studied in extraocular microvessels and in primary endothelial cell cultures from pig retina.
Surprisingly, AQP1 immunoreactivity was detected in only a small percentage of newly formed retinal microvessels, whereas AQP1 was strongly expressed in all choroidal and hyaloid vessels and in various extraocular microvessels in neonatal and prenatal mice. Oxygen-induced retinal microvessel proliferation was not significantly impaired in neonatal mice lacking AQP1, as quantified in flat-mounted retinas and thin sections. However, AQP1 was expressed in endothelial cells cultured from retinal microvessels.
Microvessel proliferation in oxygen-induced retinopathy is AQP1-independent. Retinal endothelia have the capacity to express AQP1, though intact retinal vessels chronically suppress AQP1 expression.
水通道蛋白1（AQP1）水通道在器官和肿瘤微血管内皮细胞中广泛表达。快速的微血管增殖发生在肿瘤生长、糖尿病及其他视网膜病变以及产前发育过程中。本研究的目的是探讨AQP1在视网膜血管增殖中的作用。
使用已建立的氧诱导视网膜病变小鼠模型，对野生型小鼠和AQP1基因敲除小鼠进行比较研究。将新生小鼠置于75%氧气环境中5天以抑制血管生成，然后放回室温空气中以诱导血管增殖。还对眼外微血管以及猪视网膜原代内皮细胞培养物中的AQP1表达进行了研究。
令人惊讶的是，仅在一小部分新形成的视网膜微血管中检测到AQP1免疫反应性，而在新生和产前小鼠的所有脉络膜和玻璃体血管以及各种眼外微血管中，AQP1均强烈表达。如在平铺视网膜和薄切片中所定量的，在缺乏AQP1的新生小鼠中，氧诱导的视网膜微血管增殖并未受到显著损害。然而，AQP1在从视网膜微血管培养的内皮细胞中表达。
氧诱导视网膜病变中的微血管增殖不依赖于AQP1。视网膜内皮细胞有表达AQP1的能力，尽管完整的视网膜血管长期抑制AQP1的表达。
