The role of leucine-rich alpha-2-gycoprotein 1 (Lrg1) in retinal vascular development and disease

富含亮氨酸的 α-2-糖蛋白 1 (Lrg1) 在视网膜血管发育和疾病中的作用

• 批准号: G1000466/1
• 负责人: John Greenwood
• 金额: $ 90.53万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2010
• 资助国家: 英国
• 起止时间: 2010 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G1000466%2F1
• 关键词: role; leucine; rich; alpha; gycoprotein

The uncontrolled growth of new blood vessels and damaging changes to existing blood vessels in the retina, the light sensitive part of the eye, is a major cause of blindness. These harmful changes occur in a number of different eye diseases but the most common is diabetes where loss of vision can affect up to 40% of patients. Although some advances have been made in the treatment of these conditions they still remain very difficult to control. There is therefore an urgent need to understand in much greater detail the biological mechanisms that cause these changes so that we can identify new therapeutic targets, especially during the early stages of disease, to which drugs can be developed. Our objective in this project is to investigate the role of a newly discovered molecule called Lrg1, which our preliminary data have shown to be produced at high levels by abnormal retinal blood vessels and to cause blood vessel cell proliferation. In this project we will investigate in detail how Lrg1 regulates the growth of blood vessels in the retina during normal development and how it may contribute to the development of harmful blood vessels that occur in many eye diseases. By gaining insight into the biology of this molecule we aim to validate it as a potential therapeutic target for the treatment of sight-threatening retinal vascular disease.

视网膜（眼睛的光敏感部分）中新血管不受控制的生长和现有血管的破坏性变化是失明的主要原因。这些有害的变化发生在许多不同的眼部疾病中，但最常见的是糖尿病，高达 40% 的患者会出现视力丧失。尽管在治疗这些疾病方面取得了一些进展，但它们仍然很难控制。因此，迫切需要更详细地了解导致这些变化的生物学机制，以便我们能够确定新的治疗靶点，特别是在疾病的早期阶段，从而开发药物。我们在这个项目中的目标是研究一种新发现的名为 Lrg1 的分子的作用，我们的初步数据表明，异常的视网膜血管会产生高水平的 Lrg1 分子，并导致血管细胞增殖。在这个项目中，我们将详细研究 Lrg1 在正常发育过程中如何调节视网膜血管的生长，以及它如何促进许多眼部疾病中出现的有害血管的发育。通过深入了解该分子的生物学特性，我们的目标是验证其作为治疗威胁视力的视网膜血管疾病的潜在治疗靶点。