Intravitreal injection of human CA-1 into rats, at concentrations much lower (2 ng/µl) than those measured in vitreous samples of diabetic patients (10–50 ng/µl) led to leakage of marker fluorescein dye into the intraretinal space. This was direct evidence that CA-1, in trace quantities, increases retinal vascular permeability and induces leakage. Examination of retinal ultrastructure showed intraretinal thickening, which was similar to clinically evident edema. Screening of protease pathways led the researchers to implicate kallikrein–kinin activation in this process.
糖尿病病人玻璃体样本中CA-1浓度约为10-50ng/μl,用远小于该浓度（2ng/μl）的剂量向大鼠玻璃体内注射人类CA-1蛋白，可以引起荧光素渗漏进入视网膜内。这一结果直接证明了痕量的CA-1可增加视网膜血管的通透性并导致渗漏。视网膜超微结构的检测显示视网膜增厚，这与临床明显的水肿现象相似。通过对蛋白酶通路的筛选, 研究人员发现激肽释放酶-激肽的激活参与了这个过程。
The researchers propose that retinal hemorrhage causes the release of CA-1 into the vitreous fluid from lysed red blood cells. Extracellular CA-1 mediates the hydration of CO2 released from the photoreceptor cells to bicarbonate within the vitreous. This process is normally catalyzed within the lumen of blood vessels and facilitates the removal of CO2 from the retina. The accumulated bicarbonate in the vitreous causes increasingly alkaline conditions that precede activation of the kallikrein pathway, a component of the innate inflammatory response. The outcome is the generation of bradykinin, which increases vascular permeability and inflammation.
研究人员提出视网膜出血导致CA-1从裂解的红血细胞中释放进入玻璃体液。在玻璃体中，细胞外的CA-1介导了从感光细胞释放的CO2的水合作用，形成碳酸盐。正常情况下这个反应过程是在血管管腔内被催化，可促进CO2从视网膜移除。玻璃体内累积的碳酸盐导致内环境不断碱化，进而激活了激肽释放酶通路，这一通路是炎症反应的组成部分。缓激肽作为产物，使血管通透性增加，炎症反应增强。
Although retinal hemorrhage is a common finding in people with diabetic retinopathy, Feener said, the significance of this bleeding in the pathogenesis of the disorder had not been appreciated. In essence, these experiments uncover a new pathway whereby retinal hemorrhage leads to the release of CA-1 into the vitreous, which induces kallikrein–kinin activation with a consequent increase in retinal vascular permeability and edema.
虽然视网膜出血是有糖尿病视网膜病变的病人的一种共同之处，但是Feener认为，在疾病的发病机理中出血的重要性并没有得到足够的重视。从本质上说，这些试验发现了一个新通路，那就是视网膜出血导致CA-1释放进入玻璃体,引起激肽释放酶-激肽的激活，结果导致视网膜血管通透性升高和水肿。There are 15 isoforms of CA in humans, and use of nonspecific CA inhibitors to treat conditions such as glaucoma often target more than one of them. The identification of extracellular CA-1 and its downstream mechanisms of action in diabetic retinopathy could enable development of targeted inhibitors for its treatment. Further studies in Feener’s laboratory are aimed at elucidating the role of other proteins occurring in the vitreous as a result of diabetic complications.
在人体中存在15种CA亚型，使用非特异性CA抑制剂治疗青光眼通常会作用于多个亚型。细胞外CA-1以及其在糖尿病视网膜病变中作用机制的阐明将会促进针对性抑制剂的产生。Feener实验室进一步将致力于阐明糖尿病综合症引起的玻璃体病变中其他蛋白的作用机制．

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