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/jci200522869
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发表时间：
2005-01-01
影响因子：
15.9
通讯作者：
Scott, EW
中科院分区：
文献类型：
--
作者：
Butler, JM;Guthrie, SM;Scott, EW
糖尿病性视网膜病是劳动年龄成年人失明的主要原因。它是由视网膜中的氧饥饿引起的，引起了破坏视网膜建筑的血管的异常形成。在人类中，随着增殖性糖尿病性视网膜病的进展，玻璃体基质细胞衍生的因子1（SDF-1）浓度增加。曲安赛酮患者的治疗可降低玻璃体中的SDF-1水平，并有明显的疾病改善。 SDF-1诱导人视网膜内皮细胞增加VCAM-1的表达，VCAM-1的表达是在许多造血祖细胞上发现的非常晚的抗原-4的受体，并通过降低闭塞蛋白表达来减少紧密的细胞连接。两种变化都将沿SDF-1梯度募集造血和内皮祖细胞。我们已经使用了增生性成年视网膜病的鼠模型表明，大多数是响应氧气饥饿而形成的大多数新血管起源于造血干细胞衍生的内皮祖细胞。现在，我们表明，在我们的鼠模型中诱导视网膜病变的患者中发现的SDF-1水平。玻璃体内注射对SDF-1的阻塞抗体在我们的鼠模型中也阻止了视网膜新血管形成，即使存在外源性VEGF。总之，这些数据表明SDF-1在增殖性视网膜病中起主要作用，并且可能是预防增殖性视网膜病的理想目标。
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.