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骨髓来源的细胞在小鼠病理性和生理性视网膜血管生成中具有差异参与。

Bone marrow-derived cells are differentially involved in pathological and physiological retinal angiogenesis in mice.

机构信息

Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan.

出版信息

Biochem Biophys Res Commun. 2010 Jan 8;391(2):1268-73. doi: 10.1016/j.bbrc.2009.12.057. Epub 2009 Dec 17.

Abstract

PURPOSE

Bone marrow-derived cells have been shown to play roles in angiogenesis. Although these cells have been shown to promote angiogenesis, it is not yet clear whether these cells affect all types of angiogenesis. This study investigated the involvement of bone marrow-derived cells in pathological and physiological angiogenesis in the murine retina.

MATERIALS AND METHODS

The oxygen-induced retinopathy (OIR) model was used as a retinal angiogenesis model in newborn mice. To block the influence of bone marrow-derived cells, the mice were irradiated with a 4-Gy dose of radiation from a (137)Cs source. Irradiation was performed in four different conditions with radio dense 2-cm thick lead disks; (1) H group, the head were covered with these discs to protect the eyes from radiation; (2) A group, all of the body was covered with these discs; (3) N group, mice were completely unshielded; (4) C group, mice were put in the irradiator but were not irradiated. On P17, the retinal areas showing pathological and physiological retinal angiogenesis were measured and compared to the retinas of nonirradiated mice.

RESULTS

Although irradiation induced leukocyte depletion, it did not affect the number of other cell types or body weight. Retinal nonperfusion areas were significantly larger in irradiated mice than in control mice (P<0.05), indicating that physiological angiogenesis was impaired. However, the formation of tuft-like angiogenesis processes was more prominent in the irradiated mice (P<0.05), indicating that pathological angiogenesis was intact.

CONCLUSIONS

Bone marrow-derived cells seem to be differentially involved in the formation of physiological and pathological retinal vessels. Pathological angiogenesis in the murine retina does not require functional bone marrow-derived cells, but these cells are important for the formation of physiological vessels. Our results add a new insight into the pathology of retinal angiogenesis and bolster the hypothesis that bone marrow cells are involved in the pathology or severity of retinal angiogenic diseases.

摘要

目的

骨髓来源的细胞已被证明在血管生成中发挥作用。虽然这些细胞已被证明可以促进血管生成,但尚不清楚这些细胞是否会影响所有类型的血管生成。本研究旨在探讨骨髓源性细胞在小鼠视网膜病理性和生理性血管生成中的作用。

材料和方法

采用氧诱导视网膜病变(OIR)模型作为新生小鼠视网膜血管生成模型。为了阻断骨髓源性细胞的影响,用 137Cs 源的 4Gy 剂量对小鼠进行照射。照射在四种不同条件下进行,用 2cm 厚的放射性铅盘覆盖头部,以保护眼睛免受辐射;(1)H 组,头部用这些圆盘覆盖,以保护眼睛免受辐射;(2)A 组,全身用这些圆盘覆盖;(3)N 组,老鼠完全没有屏蔽;(4)C 组,老鼠被放入辐照器但没有被辐照。在 P17,测量并比较了显示病理性和生理性视网膜血管生成的视网膜区域与未经照射的小鼠的视网膜。

结果

虽然照射诱导了白细胞耗竭,但不影响其他细胞类型的数量或体重。与对照组相比,照射组的视网膜无灌注区明显增大(P<0.05),表明生理性血管生成受损。然而,照射组的簇状血管生成过程更为明显(P<0.05),表明病理性血管生成完好。

结论

骨髓源性细胞似乎在生理性和病理性视网膜血管的形成中具有不同的作用。小鼠视网膜的病理性血管生成不需要功能性骨髓源性细胞,但这些细胞对于生理性血管的形成是重要的。我们的研究结果为视网膜血管生成的病理学提供了新的见解,并支持了骨髓细胞参与视网膜血管生成性疾病的病理或严重程度的假说。

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