Vascular and neuro-glial dysfunction in diabetic retinopathy

糖尿病视网膜病变的血管和神经胶质功能障碍

• 批准号: nhmrc : 299974
• 负责人: Prof Erica Fletcher
• 金额: $ 32.11万
• 依托单位: Monash University
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2004
• 资助国家: 澳大利亚
• 起止时间: 2004-01-01 至 2007-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/vascular-neuro-glial-diabetic-retinopathy/94434
• 关键词: Vascular; neuro; glial; dysfunction; diabetic

The retina is responsible for sight. Vision occurs by interactions between blood vessels, neurons (cells that transmit electrical signals for vision) and glia (cells that support the retina). In diabetes, high amounts of glucose in blood increases certain factors within retinal cells. These factors slowly cause damage, such that after 15 years of diabetes all patients will have some retinal disease and many will loose sight. Indeed, diabetes is the leading cause of blindness in working people. The main treatment for diabetic retinal disease is to burn away damaged blood vessels, however, this treatment has problems. Firstly, the burns destroy healthy retina and the disease continues, secondly, the treatment is performed late in the disease and therefore does not prevent the early changes in retinal cells, and thirdly, changes in neurons and glia are often not considered. Therefore, there is an urgent need to understand how blood vessels, neurons and glia interact with each other to threaten vision in diabetes, with the intention of developing safer and more effective treatments. This will be the focus of the current project. Currently, there are no studies that have examined the sequential changes in retinal blood vessels, neurons and glia in diabetes. This is mainly due to the lack of an experimental rodent model that progresses from mild to severe diabetic retinal disease. In 2003, we established such a model in the diabetic Ren-2 rat. In this project the diabetic Ren-2 rat will be used to study retinal cell changes and also to identify the factors that damage these cells. We suggest that angiotensin, bradykinin and VEGF are involved. These factors are present in the normal retina and are increased in diabetes. We will block these factors with specific drugs with the intention of understanding how these factors affect retinal cells in diabetes, and also to develop new drug therapies for the treatment of both early and late diabetic retinal disease.

视网膜负责视力。视觉是通过血管、神经元(为视觉传递电信号的细胞)和神经胶质(支持视网膜的细胞)之间的相互作用而发生的。在糖尿病患者中，血液中高含量的葡萄糖会增加视网膜细胞中的某些因子。这些因素会慢慢造成损害，以至于在糖尿病15年后，所有患者都会有一些视网膜疾病，许多人会失明。的确，糖尿病是工薪阶层失明的主要原因。糖尿病视网膜病变的主要治疗方法是烧毁受损的血管，然而，这种治疗方法存在问题。首先，烧伤破坏了健康的视网膜，疾病仍在继续；其次，治疗是在疾病后期进行的，因此无法阻止视网膜细胞的早期变化；第三，神经元和神经胶质细胞的变化通常不被考虑。因此，迫切需要了解糖尿病患者血管、神经元和神经胶质细胞如何相互作用从而威胁视力，以期开发更安全、更有效的治疗方法。这将是当前项目的重点。目前，还没有研究检测糖尿病患者视网膜血管、神经元和神经胶质细胞的顺序变化。这主要是由于缺乏从轻度糖尿病视网膜疾病发展到严重糖尿病视网膜疾病的实验性啮齿动物模型。2003年，我们在糖尿病大鼠Ren-2上建立了这样的模型。在这个项目中，糖尿病大鼠REN-2将被用来研究视网膜细胞的变化，并识别破坏这些细胞的因素。我们认为血管紧张素、缓激肽和血管内皮生长因子参与了血管紧张素转换酶的作用。这些因素存在于正常的视网膜中，在糖尿病患者中会增加。我们将用特定的药物阻断这些因素，目的是了解这些因素如何影响糖尿病的视网膜细胞，并开发治疗早期和晚期糖尿病视网膜疾病的新药物疗法。