DIETARY SUPPLEMENTS PROTECT RETINAL PIGMENT EPITHELIAL CELLS FROM APOPTOSIS

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成年人视力受损和失明的主要原因。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，我们使用粗水提取物和枸杞子的纯化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。我们正试图更好地了解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病。

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 leading cause of vision impairment and blindness in the working adult. 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 crude water 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. We 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 of the onset of the disease.