DIETARY SUPPLEMENTS PROTECT RETINAL PIGMENT EPITHELIAL CELLS FROM APOPTOSIS

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 糖尿病视网膜病变是成年人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改变是疾病进展的主要原因。视网膜色素上皮(RPE)细胞层通过提供结构和营养支持来维持视网膜的健康。高血糖会引起视网膜色素上皮的氧化应激。一种天然的植物化学混合物最近在预防氧化应激相关的眼部疾病方面受到了极大的关注，包括糖尿病视网膜病变。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，重新平衡视网膜色素上皮细胞层的细胞燃料动态平衡，作为糖尿病视网膜病变相关病理的潜在修饰物。我们发现，枸杞植物化学物质及其纯化部分，包括多糖，在体外和体内都具有增强抗氧化活性的作用。应用水溶性的枸杞植物化学物质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，我们使用枸杞的全部提取物和纯化的部分，来治疗培养中的RPE细胞和2型糖尿病小鼠。我们正在确定枸杞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，并试图更好地了解2型糖尿病小鼠内质网应激相关视网膜变性的分子机制。目前的研究结果将导致开发补充治疗方案，以预防或推迟疾病的发生。

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.