INSULIN-LIKE GROWTH FACTOR RECEPTORS IN HUMAN RETINA

拟议研究的目标是确定特定的细胞类型 它们拥有胰岛素样生长因子(IGF)的受体 并确定IGF-I和IGF-H是否与这些细胞结合 细胞在糖尿病视网膜病变中异常。总体假设是 糖尿病患者血管IGF受体的异常调节 视网膜病变(DR)。目前的建议是一项改变 我的研究计划的方向是主要强调视觉研究， 尤其是与糖尿病和新陈代谢有关的问题。 1)脑中存在GF-I和-II受体，但 在完整的视网膜中不同细胞类型之间的IGF受体 未知。我们在牛和大鼠视网膜上的初步结果表明 IGF-II受体集中在视网膜色素上皮， 脉络膜和巩膜，而IGF-I受体主要存在于 神经视网膜帮助脉络膜。拟议中的研究是一项高风险的试验 旨在确定IGF是否与特定血管或神经结合的研究 细胞在DR中发生改变。 第一个具体目标是解决这个问题：“视网膜中的哪些细胞 拥有IGF的受体？“这些方法将包括：(A) 125I-IGF-I和-II结合部位的放射自显影；(B)免疫染色 与IGF受体抗体，特别是。应用广泛的α-IR3单抗 抗人IGF-I受体和R-受体的抗体 抗大鼠IGF-11受体的II-PAB1多克隆抗血清(与 人IGF-II受体)；(C)电子显微镜研究 生物素标记的胰岛素样生长因子和EM抗受体免疫染色 抗体。 具体目标2解决了这样一个问题：“在 胰岛素样生长因子受体的数量、位置或结合特性 糖尿病视网膜病变中的特定视网膜细胞类型？ 使用DR捐赠者(男女，年龄45-70岁)从 威斯康星狮眼银行 与DR相关的血管变化最终影响最大 患有糖尿病并导致失明或视力障碍的个人 糖尿病患者合并DR的比例较高。基底的主要原因 视网膜微血管、视网膜毛细血管膜增厚 增殖和内皮细胞屏障的破坏，以及 糖尿病视网膜病变中周细胞功能尚不清楚。关于视网膜的拟议研究 生长因子受体将提高我们对细胞 糖尿病视网膜病变患者的视网膜异常。

The goals of the proposed research are to identify specific cell types which possess receptors for insulin-like growth factors (IGF's) in the human retina and to determine if binding of IGF-I and IGF-H to these cells is abnormal in diabetic retinopathy. The overall hypothesis is that vascular IGF receptors are abnormally regulated in diabetetic retinopathy (DR). The present proposal is part of a plan to change the direction of my research program to a major emphasis on vision research, particularly in relation to diabetes and metabolism. 1(GF-I and -II receptors are present in the brain but the distribution of IGF receptors among the different cell types in the intact retina is unknown. Our preliminary results on bovine and rat retinas show that IGF-II receptors are concentrated in the retinal pigment epithelium, choroid, and sclera whereas IGF-I receptors are found mainly in the neural retina aid choroid. The proposed research is a high risk pilot study aimed at determining if IGF binding to specific vascular or neural cells is altered in DR. Specific Aim No.1 addresses the question: "Which cells in the retina possess receptors for IGF's?" The methods will involve: (a) autoradiography of 125I-IGF-I and -II binding sites; (b) immunostaining with IGF receptor antibodies, esp. the widely used a-IR3 monoclonal antibody against the human IGF-I receptor for IGF-I receptors and the R- II-PAB1 polyclonal antiserum against the rat IGF-11 receptor (binds to human IGF-II receptor); (c) electron microscopic (EM) studies with biotinylated IGF'S, and EM immunostaining with the anti-receptor antibodies. Specific Aim No. 2 addresses the question, "Are there changes in numbers, location, or binding properties of IGF receptors associated with specific cell types of the retina in diabetic retinopathy?" We will use retinas from DR donors (both sexes, ages 45-70) obtained from the Lions Eye Bank, U.W. The vascular changes associated with DR eventually affect most individuals with diabetes and lead to blindness or visual impairment in a high proportion of diabetics with DR.The primary causes of basement membrane thickening in retinal microvessels, retinal capillary proliferation and the breakdown of the endothelial cell barrier and pericyte function in DR are unknown. The proposed research on retinal growth factor receptors will improve our understanding of the cellular abnormalities in the retina of patients with diabetic retinopathy.