Myeloid progenitors differentiate into microglia and promote vascular repair in a model of ischemic retinopathy
Myeloid progenitors differentiate into microglia and promote vascular repair in a model of ischemic retinopathy
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DOI：
10.1172/jci29683
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发表时间：
2006-12-01
影响因子：
15.9
通讯作者：
Friedlander, Martin
中科院分区：
文献类型：
--
作者：
Ritter, Matthew R.;Banin, Eyal;Friedlander, Martin
与缺血性疾病如早产儿视网膜病变和糖尿病视网膜病变相关的视力丧失通常是由于视网膜新生血管形成。虽然在用于治疗异常血管渗透性和增殖的化合物的开发方面已经取得了显著进展，但是这样的疗法没有解决刺激所观察到的血管生长的潜在缺氧。使用氧诱导的视网膜病变的模型，我们证明了一个人口的成人骨髓来源的骨髓祖细胞迁移到视网膜的无血管区域，分化成小胶质细胞，并促进正常化的血管。骨髓特异性缺氧诱导因子1 α（HIF-1 α）的表达是这一功能所必需的，我们还证明了内源性小胶质细胞参与视网膜血管化。这些发现表明，我们认为这是一种新的治疗方法，用于治疗缺血性视网膜病变，促进血管修复，而不是破坏。
Vision loss associated with ischemic diseases such as retinopathy of prematurity and diabetic retinopathy are often due to retinal neovascularization. While significant progress has been made in the development of compounds useful for the treatment of abnormal vascular permeability and proliferation, such therapies do not address the underlying hypoxia that stimulates the observed vascular growth. Using a model of oxygen-induced retinopathy, we demonstrate that a population of adult BM-derived myeloid progenitor cells migrated to avascular regions of the retina, differentiated into microglia, and facilitated normalization of the vasculature. Myeloid-specific hypoxia-inducible factor 1 alpha (HIF-1 alpha) expression was required for this function, and we also demonstrate that endogenous microglia participated in retinal vascularization. These findings suggest what we believe to be a novel therapeutic approach for the treatment of ischemic retinopathies that promotes vascular repair rather than destruction.