Vinores S A, Derevjanik N L, Mahlow J, Berkowitz B A, Wilson C A
Wilmer Ophthalmologic Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287-9289, USA.
Pathol Res Pract. 1998;194(7):497-505. doi: 10.1016/s0344-0338(98)80118-0.
Diabetes leads to a breakdown of the blood-retinal barrier (BRB), which can be demonstrated in experimental models by immunocytochemistry and magnetic resonance imaging (MRI). The present study utilizes these methods to investigate the mechanism of BRB breakdown in diabetic rabbits, a model ideally suited to both procedures. Rabbits were treated with alloxan and examined 2 months, 1 year, and 1.5 years after the development of diabetes to assess BRB breakdown using MRI and immunocytochemical staining for endogenous albumin. Using MRI, an increased incidence of retinal vascular leakage is first evident at 1 year of diabetes. Electron microscopic immunolocalization of albumin suggests that BRB compromise is principally mediated by transendothelial transport of serum proteins in endocytic vesicle-like structures of approximately 0.4-1 micron diameter. Some additional retinal vascular leakage is occasionally demonstrated through the interendothelial cell tight junctions, but only when adjacent vascular endothelial cells show degenerative changes. The similarity of these findings to those previously reported for diabetic humans and rats supports the use of the diabetic rabbit as a model for studying BRB dysfunction. MRI and electron microscopic (EM) immunocytochemistry are complementary methods for evaluating BRB dysfunction. MRI can provide an overall picture of the entire eye without sacrificing the animal. EM immunocytochemistry can provide a more detailed picture of a limited area of interest to gain insight into the mechanisms of extravasation. Together, both methods provide a more complete understanding of BRB breakdown in diabetic rabbits.
糖尿病会导致血视网膜屏障（BRB）破坏，这在实验模型中可通过免疫细胞化学和磁共振成像（MRI）得以证实。本研究运用这些方法来探究糖尿病兔血视网膜屏障破坏的机制，糖尿病兔模型对这两种检测方法均非常适用。给兔子注射四氧嘧啶进行治疗，并在糖尿病发病后的2个月、1年和1.5年进行检查，通过MRI和对内源性白蛋白进行免疫细胞化学染色来评估血视网膜屏障的破坏情况。使用MRI检查发现，糖尿病发病1年后视网膜血管渗漏的发生率首次明显增加。白蛋白的电子显微镜免疫定位表明，血视网膜屏障受损主要是由血清蛋白通过直径约为0.4 - 1微米的内吞小泡样结构进行跨内皮转运介导的。偶尔也会通过内皮细胞间紧密连接出现一些额外的视网膜血管渗漏，但仅在相邻血管内皮细胞出现退行性改变时才会发生。这些发现与先前报道的糖尿病患者和大鼠的结果相似，这支持将糖尿病兔作为研究血视网膜屏障功能障碍的模型。MRI和电子显微镜（EM）免疫细胞化学是评估血视网膜屏障功能障碍的互补方法。MRI可以在不牺牲动物的情况下提供整个眼睛的全貌。EM免疫细胞化学可以提供感兴趣的有限区域更详细的图像，以深入了解血管外渗的机制。这两种方法结合起来，可以更全面地了解糖尿病兔血视网膜屏障的破坏情况。
