Prevention of diabetic retinopathy by intraocular soluble flt-1 gene transfer in a spontaneously diabetic rat model.
Prevention of diabetic retinopathy by intraocular soluble flt-1 gene transfer in a spontaneously diabetic rat model.
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DOI：
10.3892/ijmm.19.1.75
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发表时间：
2007
影响因子：
5.4
通讯作者：
J. Ideno;H. Mizukami;A. Kakehashi;Yuka Saito;T. Okada;M. Urabe;A. Kume;M. Kuroki;M. Kawakami;S. Ishibashi;K. Ozawa
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文献类型：
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作者：
J. Ideno;H. Mizukami;A. Kakehashi;Yuka Saito;T. Okada;M. Urabe;A. Kume;M. Kuroki;M. Kawakami;S. Ishibashi;K. Ozawa
糖尿病患者的数量在全球范围内不断增加，糖尿病视网膜病变（DR）已成为出生后失明的最常见原因。已知血管内皮生长因子（VEGF）在DR发展过程中起核心作用。因此，抑制VEGF的作用可能阻碍疾病进展，并且可溶性VEGF受体sflt-1的基因转移是用于此目的的有吸引力的方法。然而，缺乏合适的动物模型阻碍了该策略的评估。最近，自发性糖尿病非肥胖鸟（SDT）大鼠建立，被认为是人类DR的理想模型之一。在这项研究中，我们评估了基因治疗的疗效SDT大鼠使用腺相关病毒载体（AAV-sflt-1）注射到视网膜下腔。30周后，通过荧光素血管造影术使用三个参数评估DR的进展：无血管区、广泛的高荧光素和动脉狭窄的存在。这些变化在“治疗”眼中比对照眼明显更不明显。整个研究期间未观察到不良反应。这些结果表明，局部sflt-1基因转移抑制了SDT大鼠的DR进展，并为人类DR的管理提供了强大的治疗潜力。
The number of patients suffering from diabetes mellitus is constantly rising worldwide, and diabetic retinopathy (DR) has become the most frequent cause of postnatal blindness. Vascular endothelial growth factor (VEGF) is known to play a central role during DR development. Thus, inhibiting the effects of VEGF may hamper the disease progression, and gene transfer of the soluble VEGF receptor sflt-1 is an attractive approach for this purpose. However, the lack of suitable animal models hindered the evaluation of this strategy. Recently, the spontaneously diabetic non-obese Torii (SDT) rat was established and is considered as one of the ideal models for human DR. In this study, we evaluated the efficacy of gene therapy in SDT rats by using adeno-associated viral vectors (AAV-sflt-1) injected into the subretinal space. Thirty weeks later, the progression of DR was assessed by fluorescein angiography using three parameters; the presence of an avascular area, extensive hyperfluorescein and arterial narrowing. These changes were significantly less evident in the 'treated' eyes than in the control. No adverse effects were observed throughout the study. These results indicate that local sflt-1 gene transfer inhibits DR progression in SDT rats and offers powerful therapeutic potential for the management of human DR.