DIETARY SUPPLEMENTS PROTECT RETINAL PIGMENT EPITHELIAL CELLS FROM APOPTOSIS

膳食补充剂可保护视网膜色素上皮细胞免于凋亡

• 批准号: 7959799
• 负责人: DINGBO D LIN
• 金额: $ 18.25万
• 依托单位: KANSAS STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7959799
• 关键词: Adult; Age; Animal Model; Antioxidants; Apoptosis; Blindness; Cells; Chinese Herbs; Chinese People; Computer Retrieval of Information on Scientific Projects Database; Development; Diabetes Mellitus; Diabetic Retinopathy; Diabetic mouse; Disease; Epithelial; Event; Free Radicals; Funding; Gap Junctions; Grant; Health; Healthcare; Herbal Medicine; Homeostasis; Hyperglycemia; Impairment; Institution; Lycium; Molecular; Nerve Degeneration; Nutritional Support; Oxidative Stress; Pathology; Phytochemical; Research; Research Personnel; Resources; Retina; Retinal Degeneration; Source; Structure of retinal pigment epithelium; Transgenic Organisms; United States National Institutes of Health; Vision; Water; Work; diabetic; dietary supplements; in vitro activity; in vivo; prevent

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Diabetic retinopathy is a major cause of vision impairment and blindness in working age adults. Discovery of the molecular mechanism on diabetic vision impairment is very critical for further development of healthcare treatments. The retinal pigment epithelial (RPE) cell layer is responsible for maintaining the health of the retina by providing structural and nutritional support largely through gap junctions. Hyperglycemic oxidative stress is the prime-triggering factor for the progress of the disease. RPE cell apoptosis is the primary event for diabetic retinal degeneration. We hypothesize that phytochemicals may act as potential modifiers of the pathology associated with diabetic retinopathy. PKC-gap junctional control of energy homeostasis in the retinal pigment epithelial cell layer is important for healthy vision. We have found that wolfberry extracts have high antioxidant activity in vitro. Application of water soluble wolfberry extracts prevents RPE cells from hyperglycemia/oxidative stress damage by scavenging cellular free radicals. In the current proposal, we will use the whole extracts of Chinese wolfberry, a traditional Chinese herbal medicine, to treat RPE cells in culture and diabetic mice of C57BL/6J (B6) and/or PKC¿ H101Y transgenic in a B6 background. We will determine how wolfberry extracts protect RPE cells from hyperglycemia-induced cell apoptosis through rebalance of cellular energy homeostasis by control of gap junctions. Using these two sets of animal models we will be able to investigate how control of gap junctions by dietary supplements, e.g. addition of wolfberry, protects from cell apoptosis and neuronal degeneration in diabetes in vivo.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 糖尿病视网膜病变是导致工作年龄成年人视力受损和失明的主要原因。糖尿病视力损害的分子机制的发现对进一步开发保健治疗具有重要意义。视网膜色素上皮(RPE)细胞层主要通过缝隙连接提供结构和营养支持，负责维持视网膜的健康。高血糖氧化应激是疾病进展的主要触发因素。RPE细胞凋亡是RPE的首要事件 糖尿病视网膜变性。我们假设植物化学物质可能作为糖尿病视网膜病变相关病理的潜在修饰物。蛋白激酶C-缝隙连接控制视网膜色素上皮细胞层的能量平衡对健康视力很重要。我们发现，枸杞提取物在体外具有较高的抗氧化活性。应用水溶性枸杞提取物通过清除细胞自由基来防止RPE细胞的高血糖/氧化应激损伤。在目前的方案中，我们将使用传统中草药枸杞的全部提取物来治疗培养中的RPE细胞和B6背景下的C57BL/6J(B6)和/或PKC？H101Y转基因小鼠。我们将确定枸杞提取物如何通过控制缝隙连接来重新平衡细胞能量平衡，从而保护RPE细胞免受高血糖诱导的细胞凋亡。使用这两组动物模型，我们将能够在体内研究饮食补充剂(如添加枸杞)对缝隙连接的控制如何防止糖尿病细胞凋亡和神经元变性。