Department of Ophthalmology, Yeungnam University College of Medicine, Daegu 42415, Korea.
Department of Ophthalmology, Asan Medical Center, University of Ulsan, College of Medicine, Seoul 05505, Korea.
Int J Mol Sci. 2020 Mar 20;21(6):2158. doi: 10.3390/ijms21062158.
Structural alterations of pericytes in microvessels are important features of diabetic retinopathy. Although capillary pericytes had been known not to have α-smooth muscle actin (αSMA), a recent study revealed that a specific fixation method enabled the visualization of αSMA along retinal capillaries. In this study, we applied snap-fixation in wild type and streptozotocin-induced diabetic mice to evaluate the differences in vascular smooth muscle cells of the retina and the choroid. Mice eyeballs were fixed in ice-cold methanol to prevent the depolymerization of filamentous actin. Snap-fixated retina showed αSMA expression in higher-order branches along the capillaries as well as the arterioles and venules, which were not detected by paraformaldehyde fixation. In contrast, most choriocapillaris, except those close to the arterioles, were not covered with αSMA-positive perivascular mural cells. Large choroidal vessels were covered with more αSMA-positive cells in the snap-fixated eyes. Diabetes induced less coverage of αSMA-positive perivascular mural cells overall, but they reached higher-order branches of the retinal capillaries, which was prominent in the aged mice. More αSMA-positive pericytes were observed in the choroid of diabetic mice, but the αSMA-positive expression reduced with aging. This study suggests the potential role of smooth muscle cells in the pathogenesis of age-related diabetic retinopathy and choroidopathy.
微血管周细胞的结构改变是糖尿病性视网膜病变的重要特征。尽管毛细血管周细胞以前被认为不具有α-平滑肌肌动蛋白(αSMA),但最近的一项研究表明,一种特定的固定方法可以使视网膜毛细血管上的αSMA可视化。在这项研究中,我们应用 snap 固定法在野生型和链脲佐菌素诱导的糖尿病小鼠中评估视网膜和脉络膜血管平滑肌细胞的差异。将小鼠眼球固定在冰冷的甲醇中,以防止丝状肌动蛋白的解聚。Snap 固定的视网膜在毛细血管的较高阶分支以及小动脉和小静脉中显示出 αSMA 表达,而在多聚甲醛固定中则未检测到。相比之下,除了靠近小动脉的那些之外,大多数脉络膜毛细血管没有被覆盖有 αSMA 阳性的周细胞。在 snap 固定的眼中,较大的脉络膜血管被更多的 αSMA 阳性细胞覆盖。糖尿病总体上导致覆盖的 αSMA 阳性周细胞减少,但它们到达了视网膜毛细血管的高阶分支,在老年小鼠中更为明显。糖尿病小鼠的脉络膜中观察到更多的 αSMA 阳性周细胞,但随着年龄的增长,αSMA 阳性表达减少。这项研究表明,平滑肌细胞在与年龄相关的糖尿病性视网膜病变和脉络膜病变的发病机制中可能发挥作用。