INSULIN-LIKE GROWTH FACTOR-I ACTS AS AN ANGIOGENIC AGENT IN RABBIT CORNEA AND RETINA - COMPARATIVE-STUDIES WITH BASIC FIBROBLAST GROWTH-FACTOR

INSULIN-LIKE GROWTH FACTOR-I ACTS AS AN ANGIOGENIC AGENT IN RABBIT CORNEA AND RETINA - COMPARATIVE-STUDIES WITH BASIC FIBROBLAST GROWTH-FACTOR
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DOI:
10.1007/bf00400229
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发表时间:
1993-04-01
期刊:
影响因子:
8.2
通讯作者:
GUY, J
GUY, J
中科院分区:
医学1区
文献类型:
--
作者:
GRANT, MB;MAMES, RN;GUY, J

文献摘要

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假设缺血性视网膜释放生长因子是增殖性糖尿病视网膜病变中视网膜新生血管形成的主要刺激因素。涉及的两种生长因子是胰岛素样生长因子-I 和碱性成纤维细胞生长因子。我们使用已建立的兔角膜血管生成模型(n = 30)检查了胰岛素样生长因子-I对体内新生血管形成的作用,并使用两种新的体内系统比较了胰岛素样生长因子-I和碱性成纤维细胞生长因子的作用。将超生理浓度的每种生长因子(600 微克)通过玻璃体内注射到有色素的兔子(n = 21)中,或者将填充有含有胶原蛋白和生长因子(500 ng)的乳液的多孔聚氟四乙烯室放置在视网膜表面(n = 8)。我们的结果表明,当胰岛素样生长因子-I 与缓释载体一起植入正常无血管的角膜袋中时,胰岛素样生长因子-I(10 杯/颗粒)在所有兔子中诱导血管生成。这种血管生成程度与先前显示的碱性成纤维细胞生长因子相当。对于玻璃体内研究,注射碱性成纤维细胞生长因子的眼睛中纤维化成分较多,而注射胰岛素样生长因子-I的眼睛中血管成分加重。光学和电子显微镜显示两组中都有血管增殖区域。使用胰岛素样生长因子-I和碱性成纤维细胞生长因子进行的多孔聚氟四乙烯室研究表明,室附近的血管增殖与玻璃体内注射的眼睛相似,但程度低于注射的眼睛。我们的实验总体上支持胰岛素样生长因子-I 和碱性成纤维细胞生长因子的血管生成潜力,并支持每种生长因子在增殖性糖尿病视网膜病变的发病机制中具有独特但互补的作用。
The release of growth factors from ischaemic retina has been hypothesized as the central stimulus for retinal neovascularization in proliferative diabetic retinopathy. Two of the growth factors implicated are insulin-like growth factor-I and basic fibroblast growth factor. We examined the effect of insulin-like growth factor-I on in vivo neovascularization using the established angiogenic model of the rabbit cornea (n = 30), and also compared the effects of insulin-like growth factor-I and basic fibroblast growth factor using two new in vivo systems. Either supraphysiologic concentrations of each growth factor (600 mug) were injected intravitreally into pigmented rabbits (n = 21) or porous polyfluorotetraethylene chambers filled with an emulsion containing collagen and growth factor (500 ng) were placed on the retina surface (n = 8). Our results demonstrate that when insulin-like growth factor-I was implanted together with a slow release carrier into the pocket of the normally avascular cornea, insulin-like growth factor-I (10 mug/pellet) induced angiogenesis in all rabbits. This degree of angiogenesis was comparable to that previously shown for basic fibroblast growth factor. For the intravitreal studies, the fibrotic component was greater in the basic fibroblast growth factor injected eyes, whereas the vascular component was accentuated in the eyes injected with insulin-like growth factor-I. Light and electron microscopy demonstrated areas of vascular proliferation in both groups. Porous polyfluorotetraethylene chamber studies with insulin-like growth factor-I and basic fibroblast growth factor demonstrated vascular proliferation in the vicinity of the chamber similar to the intravitreal injected eyes, but to a lesser degree than the injected eyes. Our experiments overall support the angiogenic potential of both insulin-like growth factor-I and basic fibroblast growth factor and support distinct but complimentary roles for each growth factor in the pathogenesis of proliferative diabetic retinopathy.