Novel Pathway Uncovered in Diabetic Vision Loss 糖尿病视力丧失的新机制
In people with diabetes, macular edema is a leading cause of moderate to severe vision loss. The immediate cause is increased retinal vascular permeability that allows infiltration of serum proteins and lipids into the macula. This leakage can result in thickening and interference with photoreceptor function. A study by Ben-Bo Gao, research fellow in the laboratory of Edward Feener, an HMS assistant professor of medicine at Joslin Diabetes Center, identifies a novel pathway involved in development of retinal vascular permeability and activation of the kallikrein?Ckinin system. The findings appear in the Jan. 28 online edition of Nature Medicine. (Nature Medicine - 13, 181 - 188 (2007)
黄斑水肿是导致糖尿病病人视力中度至重度丧失的主要原因。视网膜血管通透性增高引起的血浆蛋白和脂质渗透进入黄斑是导致黄斑水肿直接原因，这种渗漏作用导致视网膜的增厚以及感光功能受到影响。高本波博士是Edward Feener实验室的研究人员,Feener博士是哈佛大学医学院Joslin糖尿病中心的医学助理教授。高本波博士进行的一项研究中发现与视网膜血管通透性增高及激肽释放酶-激肽系统的激活有关的新的机制。这一研究结果已经在１月28日的《自然医学》杂志上刊登。
Using mass spectrometry?Cbased proteomics, Gao, Feener, and their colleagues identified 27 proteins from vitreous samples of patients with diabetic retinopathy whose levels were elevated over those of the same proteins in non-diabetic controls. The researchers homed in on carbonic anhydrase-1 (CA-1) for further study since its level was 15-fold higher than that in samples from non-diabetic controls. The scientists predicted that an overabundance of its activity in the vitreous might interfere with extracellular pH homeostasis in the neuroretina.
用基于质谱分析的蛋白质组学技术，高博士,Feener博士和他们的同事从有糖尿病视网膜病变病人的玻璃体样本中找到了27种表达高于非糖尿病组的蛋白。其中碳酸酐酶（CA-1)的水平比非糖尿病组高15倍,研究人员进一步研究了这种蛋白。他们发现在玻璃体中它的活性过高会影响到神经视网膜的细胞外的PH值的稳态。
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?C50 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?Ckinin activation in this process.
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