Expression of apoptosis markers in the retinas of human subjects with diabetes
Expression of apoptosis markers in the retinas of human subjects with diabetes
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DOI：
10.1167/iovs.03-1392
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发表时间：
2004-08-01
影响因子：
4.4
通讯作者：
Geboes, K
中科院分区：
文献类型：
--
作者：
Abu El-Asrar, AM;Dralands, L;Geboes, K
目的.研究糖尿病患者视网膜中凋亡介质的表达。检查了来自5名糖尿病受试者的10只供体眼睛和来自4名无已知眼部疾病的非糖尿病受试者的8只眼睛作为对照。采用免疫组化方法检测胶质细胞酸性蛋白（GFAP）、caspase-3、Fas、Fas配体（FasL）、Bax、Bcl-2、survivin、p53、细胞外信号调节激酶（ERK 1/2）和p38的表达。在所有无糖尿病受试者的视网膜中，弱Bcl-2免疫反应仅限于神经纤维层中的GFAP阳性胶质细胞。ERK 1/2的弱免疫反应性在内核层的少数细胞核和少数Muller细胞突起中被注意到。在视网膜色素上皮细胞中观察到Survivin的胞浆免疫染色。检测的其他抗体无免疫反应性。所有糖尿病视网膜显示神经节细胞中caspase-3、Fas和Bax的胞浆免疫反应。FasL免疫反应在GFAP阳性细胞中表达。Bcl-2免疫反应性的上调，注意到在神经纤维和神经节细胞层的GFAP阳性细胞，和Bcl-2的诱导，注意到在Muller细胞的过程。在神经纤维和神经节细胞层的内核层、GFAP阳性细胞和许多Muller细胞突起中的许多细胞核中观察到ERK 1/2的强免疫反应性。Survivin免疫反应性在糖尿病视网膜中没有改变。p53和p38均为阴性。糖尿病视网膜中的神经节细胞表达几种促凋亡分子，表明这些细胞是最脆弱的群体。糖尿病视网膜中的神经胶质细胞被激活并表达除了细胞毒性效应分子FasL之外的几种抗凋亡分子，这表明神经胶质细胞在诱导神经节细胞凋亡中的可能作用。
PURPOSE. To investigate the expression of the apoptotic mediators in the retinas from human subjects with diabetes mellitus.METHODS. Ten donor eyes from five subjects with diabetes mellitus, and eight eyes from four nondiabetic subjects without known ocular disease serving as control subjects were examined. Immunohistochemical techniques were used with antibodies directed against glial fibrillary acidic protein (GFAP), caspase-3, Fas, Fas ligand (FasL), Bax, Bcl-2, survivin, p53, extracellular signal-regulated kinases (ERK1/2), and p38.RESULTS. In retinas from all subjects without diabetes, weak Bcl-2 immunoreactivity was confined to GFAP-positive glial cells in the nerve fiber layer. Weak immunoreactivity for ERK1/2 was noted in a few nuclei in the inner nuclear layer and in a few Muller cell processes. Cytoplasmic immunostaining for survivin was noted in the retinal pigment epithelial cells. There was no immunoreactivity for the other antibodies tested. All diabetic retinas showed cytoplasmic immunoreactivity for caspase-3, Fas, and Bax in ganglion cells. FasL immunoreactivity was detected in GFAP-positive cells. Upregulation of Bcl-2 immunoreactivity was noted in GFAP-positive cells in nerve fiber and ganglion cell layers, and Bcl-2 induction was noted in Muller cell processes. Strong immunoreactivity for ERK1/2 was observed in many nuclei in the inner nuclear layer in GFAP-positive cells in the nerve fiber and ganglion cell layers and numerous Muller cell processes. Survivin immunoreactivity was not altered in the diabetic retinas. There was no immunoreactivity for p53 and p38.CONCLUSIONS. Ganglion cells in diabetic retinas express several proapoptosis molecules, suggesting that these cells are the most vulnerable population. Glial cells in diabetic retinas are activated and express several antiapoptosis molecules in addition to the cytotoxic effector molecule FasL, suggesting a possible role of glial cells in induction of apoptosis in ganglion cells.