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: 8360338
• 负责人: DINGBO D LIN
• 金额: $ 8.67万
• 依托单位: KANSAS STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8360338
• 关键词: Adult; Antioxidants; Apoptosis; Attention; Blindness; Cell Survival; Cells; Development; Diabetic Retinopathy; Diabetic mouse; Disease; Disease Progression; Epithelial; Eye diseases; Free Radicals; Funding; Grant; Health; Homeostasis; Hyperglycemia; Impairment; Lead; Lycium; Molecular; National Center for Research Resources; Nutritional Support; Onset of illness; Outcome; Oxidative Stress; Pathology; Phytochemical; Prevention; Principal Investigator; Regimen; Regulation; Research; Research Infrastructure; Resources; Retina; Retinal; Retinal Degeneration; Retinal Pigments; Signal Pathway; Source; Structure of retinal pigment epithelium; Therapeutic; United States National Institutes of Health; Vision; Water; Work; cost; dietary supplements; endoplasmic reticulum stress; 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. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Diabetic retinopathy is a major cause of vision impairment and blindness in the working adult. Mechanistic studies show that oxidative stress and subsequent alteration of signaling pathways are the primarily causal factors in the disease progression. The retinal pigment epithelial (RPE) cell layer is responsible for maintaining the health of the retina by providing structural and nutritional support. Hyperglycemia would cause oxidative stress in the retinal pigment epithelium. A natural mixture of phytochemicals has received much recent attention in prevention of oxidative stress-related eye diseases, including diabetic retinopathy. We hypothesize that wolfberry phytochemicals may act as potential modifiers of the pathology associated with diabetic retinopathy through simultaneous regulation of cell survival/apoptosis pathways, rebalance of cellular fuel homeostasis in the retinal pigment epithelial cell layer. We have found that wolfberry phytochemicals, and its purified fractions, including polysacchardies, have enhanced antioxidant activity in vitro and in vivo. Application of water soluble wolfberry phytochemicals prevents RPE cells from hyperglycemia/oxidative stress damage by scavenging cellular free radicals. In the current proposal, we use both whole extracts and the purified fractions of wolfberry, to treat RPE cells in culture and type 2 diabetic mice. We are determining how wolfberry bioactive compounds protect RPE and/or other retinal cells from hyperglycemia-induced cell apoptosis, are trying to better understand the molecular mechanism on endoplasmic reticulum stress-related retinal degeneration in the type 2 diabetic mouse. The outcome of the current study will lead to the development of complementary therapeutic regimens for prevention or delay the onset of the disease.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 糖尿病性视网膜病变是成年工作者视力受损和失明的主要原因。机制研究表明，氧化应激和随后的信号通路的改变是疾病进展的主要原因。视网膜色素上皮（RPE）细胞层负责通过提供结构和营养支持来维持视网膜的健康。 高血压会引起视网膜色素上皮细胞的氧化应激。植物化学物质的天然混合物最近在预防氧化应激相关的眼部疾病（包括糖尿病视网膜病变）方面受到了广泛关注。我们推测枸杞植物化学物质可能通过同时调节细胞存活/凋亡途径、视网膜色素上皮细胞层中细胞燃料稳态的再平衡来作为与糖尿病视网膜病变相关的病理学的潜在修饰剂。我们已经发现，枸杞植物化学物质，及其纯化的馏分，包括多糖，在体外和体内具有增强的抗氧化活性。水溶性枸杞植物化学物质的应用通过清除细胞自由基来防止RPE细胞受到高血糖/氧化应激损伤。在目前的建议中，我们使用枸杞的整个提取物和纯化部分来治疗培养物和2型糖尿病小鼠中的RPE细胞。我们正在确定枸杞生物活性化合物如何保护RPE和/或其他视网膜细胞免受高血糖诱导的细胞凋亡，试图更好地了解2型糖尿病小鼠内质网应激相关视网膜变性的分子机制。目前研究的结果将导致开发用于预防或延迟疾病发作的补充治疗方案。