Wang Qian, Gorbey Stefan, Pfister Frederick, Höger Simone, Dorn-Beineke Andrea, Krügel Katja, Berrone Elena, Wu Liang, Korff Thomas, Lin Jihong, Busch Stefanie, Reichenbach Andreas, Feng Yuxi, Hammes Hans-Peter
V Medical Department, Medical Faculty Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany.
Cell Physiol Biochem. 2011;27(6):769-82. doi: 10.1159/000330085. Epub 2011 Jun 17.
BACKGROUND/AIMS: Diabetic retinopathy is characterized by pericyte loss and vasoregression both in the clinic and in animal models. A mild neurodegeneration with loss of ganglion cells is also described in the diabetic retina. Like VEGF-A, Epo is angioprotective and, in high doses, neuroprotective, however, without affecting vessel permeability. This study was to investigate the effect of a long-term suberythropoietic dose of Epo on vascular damage and neurodegeneration in a rat model of diabetic retinopathy.
We administered Epo 3x256 IU/kg body weight/week to streptozotocin-diabetic Wistar rats for up to 6 months. Leukostasis was analyzed by quantitation of CD45 positive cells adherent to the retinal microvasculature. VEGF-A levels were assessed by Elisa at 3 months of treatment. Vasoregression was quantified in retinal digest preparations after 6 months of Epo treatment. Neurodegeneration was analyzed from PAS stained retinal paraffin preparations.
Leukostasis was unaffected by treatment with Epo which significantly inhibited the loss of pericyte and the formation of acellular capillaries. Neurodegeneration in the diabetic retina was significantly reduced by Epo treatment. Increased VEGF-A levels in the diabetic retina were normalized by Epo treatment.
Suberythropoietic Epo is effective to protect microvascular and neuronal damage in the experimental diabetic retina.
背景/目的：糖尿病视网膜病变在临床和动物模型中均表现为周细胞丢失和血管消退。糖尿病视网膜中还存在轻度神经变性，伴有神经节细胞丢失。与血管内皮生长因子A（VEGF-A）一样，促红细胞生成素（Epo）具有血管保护作用，高剂量时还具有神经保护作用，但不影响血管通透性。本研究旨在探讨长期给予低于促红细胞生成剂量的Epo对糖尿病视网膜病变大鼠模型血管损伤和神经变性的影响。
我们每周给链脲佐菌素诱导的糖尿病Wistar大鼠腹腔注射Epo，剂量为3×256 IU/kg体重，持续6个月。通过定量粘附于视网膜微血管的CD45阳性细胞分析白细胞淤滞情况。在治疗3个月时通过酶联免疫吸附测定（ELISA）评估VEGF-A水平。在Epo治疗6个月后，对视网膜消化制剂中的血管消退情况进行定量分析。从过碘酸雪夫（PAS）染色的视网膜石蜡制剂中分析神经变性情况。
Epo治疗对白细胞淤滞无影响，但能显著抑制周细胞丢失和无细胞毛细血管的形成。Epo治疗可显著减轻糖尿病视网膜中的神经变性。Epo治疗可使糖尿病视网膜中升高的VEGF-A水平恢复正常。
低于促红细胞生成剂量的Epo可有效保护实验性糖尿病视网膜中的微血管和神经元损伤。
