Mizutani M, Gerhardinger C, Lorenzi M
Schepens Eye Research Institute and Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts 02114, USA.
Diabetes. 1998 Mar;47(3):445-9. doi: 10.2337/diabetes.47.3.445.
Vascular cells may not be the only cells affected by diabetes in the retina. In particular, abnormalities of the b-wave of the electroretinogram in diabetic patients with absent or minimal microangiopathy have pointed to possible dysfunction of Müller cells, the principal glia of the retina. In this study, we sought evidence for diabetes-induced Müller cell abnormalities by testing the expression of three proteins (Bcl-2, glutamine synthetase [GS], and glial fibrillar acidic protein [GFAP]) that are solely or predominantly expressed in Müller cells and show a reproducible pattern of changes in the context of retinal injuries or degenerations. Retinas obtained postmortem from a total of 14 donors aged 65 +/- 6 years with 10 +/- 4 years of diabetes and histological evidence of microangiopathy and 18 age-matched nondiabetic donors were examined by immunohistochemistry and immunoblotting. The typical Müller cell pattern of Bcl-2 and GS immunostaining was similar for both intensity and distribution in the nondiabetic and diabetic retinas, as were the levels of the two proteins. In contrast, GFAP staining, largely confined to the most proximal retina in the nondiabetic donors, was in most diabetic retinas present along the entire length of the Müller cell processes, throughout the outer retina. Accordingly, the level of GFAP was increased in the diabetic retinas (161 +/- 106 densitometric units/microg protein vs. 55 +/- 45 in the nondiabetic retinas, P = 0.03). These data provide evidence for selective biosynthetic changes of Müller glial cells in diabetes. Because Müller cells produce factors capable of modulating blood flow, vascular permeability, and cell survival, and their processes surround all blood vessels in the retina, a possible role of these cells in the pathogenesis of retinal microangiopathy deserves to be investigated.
血管细胞可能并非视网膜中唯一受糖尿病影响的细胞。特别是，在无微血管病变或仅有轻微微血管病变的糖尿病患者中，视网膜电图b波异常表明 Müller 细胞（视网膜主要的神经胶质细胞）可能存在功能障碍。在本研究中，我们通过检测三种仅在 Müller 细胞中表达或主要在 Müller 细胞中表达的蛋白质（Bcl-2、谷氨酰胺合成酶[GS]和胶质纤维酸性蛋白[GFAP]）的表达情况，来寻找糖尿病诱导的 Müller 细胞异常的证据，这些蛋白质在视网膜损伤或退化的情况下会呈现出可重复的变化模式。对总共14名年龄在65±6岁、患有10±4年糖尿病且有微血管病变组织学证据的供体以及18名年龄匹配的非糖尿病供体的死后视网膜进行了免疫组织化学和免疫印迹检查。非糖尿病和糖尿病视网膜中 Bcl-2 和 GS 免疫染色的典型 Müller 细胞模式在强度和分布上相似，这两种蛋白质的水平也是如此。相比之下，GFAP 染色在非糖尿病供体中主要局限于视网膜最靠近近端的部分，而在大多数糖尿病视网膜中，沿着 Müller 细胞突起的全长，贯穿外视网膜均有出现。因此，糖尿病视网膜中 GFAP 的水平升高（光密度单位/微克蛋白为161±106，而非糖尿病视网膜中为55±45，P = 0.03）。这些数据为糖尿病中 Müller 神经胶质细胞的选择性生物合成变化提供了证据。由于 Müller 细胞产生的因子能够调节血流、血管通透性和细胞存活，且其突起环绕着视网膜中的所有血管，因此这些细胞在视网膜微血管病变发病机制中的可能作用值得研究。
