SDF-1 is both necessary and sufficient to promote proliferative retinopathy.
SDF-1 is both necessary and sufficient to promote proliferative retinopathy.
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DOI：
10.1172/jci22869
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发表时间：
2005-01
期刊：
影响因子：
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通讯作者：
J. Butler;Steven M. Guthrie;M. Koç;A. Afzal;S. Caballero;H. Brooks;R. Mames;M. Segal;M. Grant-M.-Gran
中科院分区：
文献类型：
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作者：
J. Butler;Steven M. Guthrie;M. Koç;A. Afzal;S. Caballero;H. Brooks;R. Mames;M. Segal;M. Grant-M.-Gran
糖尿病视网膜病变是导致工作年龄成人失明的主要原因。它是由视网膜中的氧饥饿引起的，其诱导破坏视网膜结构的血管的异常形成。在人类中，玻璃体基质细胞衍生因子-1（SDF-1）浓度随着增殖性糖尿病视网膜病变的进展而增加。用曲安西龙治疗患者可降低玻璃体中的SDF-1水平，并显著改善疾病。SDF-1诱导人视网膜内皮细胞增加VCAM-1的表达，VCAM-1是一种在许多造血祖细胞上发现的极晚期抗原-4的受体，并通过减少occludin表达来减少细胞紧密连接。这两种变化都将用于沿SDF-1梯度沿着募集造血和内皮祖细胞。我们已经表明，使用增殖性成人视网膜病变的小鼠模型，大多数新血管形成的反应，氧饥饿起源于造血干细胞衍生的内皮祖细胞。我们现在表明，在增殖性视网膜病变患者中发现的SDF-1水平在我们的小鼠模型中诱导视网膜病变。在我们的小鼠模型中，玻璃体内注射SDF-1阻断抗体可预防视网膜新生血管形成，即使在存在外源性VEGF的情况下也是如此。总之，这些数据表明，SDF-1在增殖性视网膜病变中起着重要作用，可能是预防增殖性视网膜病变的理想靶点。
Diabetic retinopathy is the leading cause of blindness in working-age adults. It is caused by oxygen starvation in the retina inducing aberrant formation of blood vessels that destroy retinal architecture. In humans, vitreal stromal cell-derived factor-1 (SDF-1) concentration increases as proliferative diabetic retinopathy progresses. Treatment of patients with triamcinolone decreases SDF-1 levels in the vitreous, with marked disease improvement. SDF-1 induces human retinal endothelial cells to increase expression of VCAM-1, a receptor for very late antigen-4 found on many hematopoietic progenitors, and reduce tight cellular junctions by reducing occludin expression. Both changes would serve to recruit hematopoietic and endothelial progenitor cells along an SDF-1 gradient. We have shown, using a murine model of proliferative adult retinopathy, that the majority of new vessels formed in response to oxygen starvation originate from hematopoietic stem cell-derived endothelial progenitor cells. We now show that the levels of SDF-1 found in patients with proliferative retinopathy induce retinopathy in our murine model. Intravitreal injection of blocking antibodies to SDF-1 prevented retinal neovascularization in our murine model, even in the presence of exogenous VEGF. Together, these data demonstrate that SDF-1 plays a major role in proliferative retinopathy and may be an ideal target for the prevention of proliferative retinopathy.