Capillary Shunts in the Pathogenesis of Diabetic Retinopathy
Capillary Shunts in the Pathogenesis of Diabetic Retinopathy
复制标题
糖尿病视网膜病变发病机制中的毛细血管分流
作者：
I. Leopold
在本期中，Cogan 和 Kuwabara 提出了鬼影出现和视网膜毛细血管壁壁细胞缺失与微动脉瘤存在之间的关系。随着新的胰蛋白酶消化方法的开发以及随后用合适的染料染色，这些研究人员已经鉴定出与毛细血管壁相关的两种类型的细胞。一种是管腔内壁的内皮细胞；另一种是内皮细胞。他们将另一种类型称为壁细胞，因为它被包裹在血管壁内，并且其内表面和外表面都被基底膜覆盖。他们无法在其他地方的毛细血管上找到这些壁细胞，例如：结缔组织、结膜或脉络膜。他们也无法在病理性增殖到人类玻璃体的血管中找到这些壁细胞。 Cogan 和 Kuwabara 将壁细胞与周细胞区分开来，他们最初将其识别为血管周围神经胶质细胞，将周细胞一词限制为壁外的细胞，这与术语（壁细胞）相反，壁细胞指的是壁物质内的细胞。所定义的周细胞，如果存在的话，不受毛细血管壁的保护，会在制作整个视网膜之前被胰蛋白酶消化掉，并且在其制备物中不会被看到。有人认为，这些所谓的壁细胞即使不相同，也可能与 Bloom 和 Fawcett 描述的其他身体毛细血管的所谓未分化细胞相似。尽管在人眼中病理性发育成玻璃体的血管不显示壁细胞，但穆特鲁和利奥波德发现它们排列在构成人类胎儿眼睛正常玻璃体循环的毛细血管内。早在十六周龄的标本中就观察到了这些现象。 Cogan 和 Kuwabara 假设壁细胞在视网膜毛细血管功能中发挥着重要作用，因为它们在所有研究的哺乳动物视网膜中广泛存在和丰富，例如哺乳动物视网膜。人、猴、猫、狗、仓鼠、小鼠和大鼠。 1961年，Cogan、Touissant和Kuwabara推测壁细胞的局灶性变性可能是糖尿病视网膜病变的最初病变。大多数研究人员怀疑毛细血管变性是糖尿病性视网膜病变的最初发生，并推测视网膜毛细血管病变是糖尿病全身性微血管病变的一部分。 Cogan 等人的观察。可以解释毛细血管的局部受累，尤其是眼睛的毛细血管。糖尿病患者的许多身体毛细血管中都出现了基底膜的变化。视网膜和肾毛细血管的基底膜明显增厚，肌肉和皮肤毛细血管的基底膜也明显增厚。这通过光学显微镜和电子显微镜都可以明显看出。 Yamashita 和 Becker 报道了糖尿病患者人眼睫状突基底膜的类似增厚情况。正如布拉德沃斯等人所指出的，毛细血管病的最初病变可能是视网膜、肾小球、肌肉和皮下组织毛细血管的基底膜增厚。这一观察是在临床糖尿病建立之前对患者进行的。也许内皮细胞是造成基底膜过度产生的原因。位于细胞壁范围内和增厚的基底膜内的所谓壁细胞或周细胞的功能尚不清楚。与微动脉瘤相关的大毛细血管通道中壁细胞的缺失可能是继发于基底膜变化的。事件的顺序并不确定。有关这些细胞的光和电子显微镜外观的信息是可用的。壁细胞的细胞质含量与内皮细胞相似，但含量少得多。内皮细胞彼此连续，壁细胞不连续。两者似乎都源自相同的原基，但内皮细胞产生得更早。组织化学染色已证明乳酸 DPN 具有脱氢酶活性，并且几乎没有磷酸酶、胆碱酯酶或琥珀酸脱氢酶活性（如果有的话）。壁细胞可能具有从大部分毛细血管中排除红细胞的功能，Cogan 和 Kuwabara 也表明抑制新生血管形成
In the present issue, Cogan and Kuwabara suggest a relationship between the ghost appearance and absence of mural cells in the walls of the retinal capillaries and the presence of microaneurysms. With the development of a new trypsin digest method and subsequent staining by suitable dyes, these investigators have identified two types of cells associated with the capillary wall. One type is the endothelial cell lining the lumen; the other type they have called the mural cell because it is encased within the vessel wall and covered on both its inner and outer surfaces by basement membrane. They have not been able to find these mural cells on capillaries elsewhere, e.g. connective tissue, conjunctiva or choroid. They also could not find these mural cells in vessels that proliferate pathologically into the vitreous of man. Cogan and Kuwabara have distinguished the mural cell, which they initially identified as a perivascular glial cell, from the pericyte, limiting the term of pericyte to cells outside the wall in contradistinction to the term (mural cell) which refers to cells within the substance of the wall. Pericytes as defined, unprotected by the wall of the capillary if present, would be digested away by the trypsin prior to making the whole mount of the retina and would not be seen in their preparations. It has been suggested that these so-called mural cells may be similar, if not identical, to the so-called undifferentiated cell of the other body capillaries described by Bloom and Fawcett. Although the vessels which pathologically develop into the vitreous in the human eye do not show mural cells, Mutlu and Leopold have seen them lining the capillaries that make up the normal hyaloid circulation of the eye of the human fetus. These have been observed in specimens as early as sixteen weeks of age. Cogan and Kuwabara have assumed that the mural cells play a significant role in the retinal capillary function because of their widespread occurrence and abundance in all mammalian retinas studied, e.g. man, monkey, cat, dog, hamster, mouse and rat. In 1961, Cogan, Touissant and Kuwabara postulated that focal degeneration of the mural cells may be the initial lesion in diabetic retinopathy. Most investigators suspect that capillary degeneration is the initial incident in diabetic retinopathy and speculate that the retinal capillary disease is part of a body-wide microangiopathy of diabetes mellitus. The observation of Cogan et al. could explain the focal involvement of the capillaries, particularly those of the eye. Basement membrane changes have been described in many body capillaries of patients with diabetes mellitus. The basement membrane is definitely thickened in the retinal and renal capillaries, also in the muscle and skin capillaries. This has been evident by both light and electron microscopy. Yamashita and Becker have reported a similar thickening of the basement membrane of the ciliary processes of the human eye of patients with diabetes mellitus. Perhaps the initial lesion of the capillary microangiopathy is, as suggested by Bloodworth and others, the thickening of the basement membrane in the capillaries of the retina, of the glomerulus, of muscle and subcutaneous tissue. This observation has been made in patients before the establishment of clinical diabetes. Perhaps the endothelial cell is responsible for this overproduction of basement membrane. The function of the so-called mural cell or pericyte lying within the confines of the cell wall and within the thickening basement membrane is not known. The absence of mural cells in the large capillary channels associated with microaneurysms may be secondary to the basement membrane changes. The sequence of events is not certain. Information is available on the light and electron microscopic appearance of these cells. Cytoplasmic contents of the mural cells are similar but much scantier than that of the endothelial cells. The endothelial cells are continuous with each other and the mural cells are discontinuous. Both appear to arise from the same anlage but the endothelial cells arise earlier. Histochemical stains have demonstrated dehydrogenase activity for lactate DPN and little, if any, phosphatase, cholinesterase or succinic dehydrogenase activity. The mural cells may have the function of excluding red blood cells from most of the capillaries and Cogan and Kuwabara also suggest that inhibition of neovasculariza-