Ash John, McLeod D Scott, Lutty Gerard A
Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Mol Vis. 2005 Apr 28;11:298-308.
Vascular development in the eye has been described as a complex process involving both vasculogenesis and angiogenesis. Multiple cell types are involved in the process including angioblasts, vascular endothelial cells, astrocytes, pericytes, and Muller glial cells. This suggests that multiple growth factors and cytokines are required to regulate retinal vascular development. Leukemia inhibitory factor (LIF) is a member of the interleukin 6 family of cytokines. LIF is expressed during inflammation and has been reported to affect vascular development in culture; however, its effects in vivo have not been demonstrated. The purpose of this study was to determine how LIF could regulate ocular vascular development.
We have analyzed ocular vascular development in transgenic mice that express LIF in the ocular lens from embryonic day 11.
In transgenic mice, LIF reduced development of embryonic vasculature in the eye, and inhibited retinal vascular development. Inhibition in vivo was independent of vascular endothelial cell growth factor (VEGF) expression. In older transgenic mice, the absence of a retinal vasculature resulted in retinal ischemia and elevated VEGF levels. The upregulation of VEGF resulted in the proliferation of pathological vascular membranes in the vitreous and neovascularization penetrating the retina, which in turn resulted in tractional retinal detachment.
LIF is a potent inhibitor of retinal vascular development. These transgenic mice will be useful as a model of persistent fetal vasculature and to study the mechanism for the development of neovascular membranes in the vitreous and could be used to develop inhibitors of tractional detachment.
眼部血管发育被描述为一个涉及血管生成和血管新生的复杂过程。多种细胞类型参与这一过程，包括成血管细胞、血管内皮细胞、星形胶质细胞、周细胞和米勒胶质细胞。这表明需要多种生长因子和细胞因子来调节视网膜血管发育。白血病抑制因子（LIF）是细胞因子白细胞介素6家族的成员。LIF在炎症过程中表达，据报道在培养中会影响血管发育；然而，其在体内的作用尚未得到证实。本研究的目的是确定LIF如何调节眼部血管发育。
我们分析了从胚胎第11天开始在晶状体中表达LIF的转基因小鼠的眼部血管发育情况。
在转基因小鼠中，LIF减少了眼部胚胎血管的发育，并抑制了视网膜血管发育。体内抑制作用独立于血管内皮生长因子（VEGF）的表达。在年龄较大的转基因小鼠中，视网膜血管缺失导致视网膜缺血和VEGF水平升高。VEGF的上调导致玻璃体中病理性血管膜增生和新生血管穿透视网膜，进而导致牵拉性视网膜脱离。
LIF是视网膜血管发育的有效抑制剂。这些转基因小鼠可作为持续性胎儿血管模型，用于研究玻璃体中新生血管膜的形成机制，并可用于开发牵拉性脱离的抑制剂。
