Altered expression of retinal occludin and glial fibrillary acidic protein in experimental diabetes. The Penn State Retina Research Group.
Altered expression of retinal occludin and glial fibrillary acidic protein in experimental diabetes. The Penn State Retina Research Group.
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发表时间：
2000-10
影响因子：
4.4
通讯作者：
A. Barber;D. Antonetti;T. Gardner
中科院分区：
文献类型：
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作者：
A. Barber;D. Antonetti;T. Gardner
目的 研究糖尿病如何改变血视网膜屏障 (BRB) 处的血管内皮细胞紧密连接蛋白和神经胶质细胞形态。方法 通过免疫荧光组织化学方法，在链脲佐菌素 (STZ) 糖尿病大鼠和年龄匹配对照大鼠以及 BB/Wor 糖尿病易感大鼠和年龄匹配糖尿病抵抗大鼠的平贴视网膜中，探讨神经胶质标记物、胶质纤维酸性蛋白 (GFAP) 和内皮细胞紧密连接蛋白 occludin 的分布。结果 GFAP 免疫反应性仅限于对照视网膜中的星形胶质细胞。两个月的 STZ 糖尿病降低了星形胶质细胞中的 GFAP 免疫反应性，并增加了小群 Müller 细胞中的 GFAP 免疫反应性。 STZ 诱导糖尿病 4 个月后，所有 Müller 细胞都具有强烈的 GFAP 免疫反应性，而星形胶质细胞中几乎没有。 BB/Wor 糖尿病大鼠的 GFAP 免疫反应性也有类似的变化。正常大鼠的 Occludin 免疫反应性在外丛状层的毛细血管床和内视网膜的小动脉中最强，但在毛细血管后微静脉中的强度要低得多。糖尿病降低了毛细血管中的occludin免疫反应性，并诱导小动脉中从连续细胞边界到中断的点状免疫反应性的重新分布。 48 小时的胰岛素治疗逆转了 STZ 糖尿病大鼠的 GFAP 和 occludin 免疫反应模式。结论 糖尿病改变了视网膜神经胶质细胞中 GFAP 的表达，同时伴随着内皮细胞中 occludin 的减少和重新分布。这些变化与 BRB 处神经胶质-内皮细胞相互作用的改变导致糖尿病视网膜病变的概念是一致的。
PURPOSE To investigate how diabetes alters vascular endothelial cell tight junction protein and glial cell morphology at the blood-retinal barrier (BRB). METHODS The distribution of the glial marker, glial fibrillary acidic protein (GFAP), and the endothelial cell tight junction protein occludin were explored by immunofluorescence histochemistry in flatmounted retinas of streptozotocin (STZ)-diabetic and age-matched control rats, and in BB/Wor diabetes-prone and age-matched diabetes-resistant rats. RESULTS GFAP immunoreactivity was limited to astrocytes in control retinas. Two months of STZ-diabetes reduced GFAP immunoreactivity in astrocytes and increased GFAP immunoreactivity in small groups of Müller cells. After 4 months of STZ-induced diabetes, all Müller cells had intense GFAP immunoreactivity, whereas there was virtually none in the astrocytes. BB/Wor diabetic rats had similar changes in GFAP immunoreactivity. Occludin immunoreactivity in normal rats was greatest in the capillary bed of the outer plexiform layer and arterioles of the inner retina but much less intense in the postcapillary venules. Diabetes reduced occludin immunoreactivity in the capillaries and induced redistribution from continuous cell border to interrupted, punctate immunoreactivity in the arterioles. Forty-eight hours of insulin treatment reversed the pattern of GFAP and occludin immunoreactivity in the STZ-diabetic rats. CONCLUSIONS Diabetes alters GFAP expression in retinal glial cells, accompanied by reduction and redistribution of occludin in endothelial cells. These changes are consistent with the concept that altered glial-endothelial cell interactions at the BRB contribute to diabetic retinopathy.