PDF(Pubmed)
Abstract：
Previously, the RXR agonist UAB126 demonstrated therapeutic potential to treat obese mice by controlling blood glucose levels (BGL) and altering the expression of genes associated with lipid metabolism and inflammatory response. The purpose of the study was to assess the effects of UAB126 on the progression of diabetic retinopathy (DR) in rodent models of type 1 diabetes (T1D), streptozotocin-induced, and type 2 diabetes (T2D), in db/db mice. UAB126 treatment was delivered either by oral gavage for 6 weeks or by topical application of eye drops for 2 weeks. At the end of the treatment, the retinal function of diabetic mice was assessed by electroretinography (ERG), and their retinal tissue was harvested for protein and gene expression analyses. Bone-marrow cells were isolated and differentiated into bone marrow-derived macrophages (BMDMs). The glycolysis stress test and the 2-DG glucose uptake analysis were performed. Our results demonstrated that in the UAB126-treated diabetic BMDMs, the ECAR rate and the 2-DG uptake were improved as compared to untreated diabetic BMDMs. In UAB126-treated diabetic mice, hyperglycemia was reduced and associated with the preservation of ERG amplitudes and enhanced AMPK activity. Retinas from diabetic mice treated with topical UAB126 demonstrated an increase in Rxr and Ppar and the expression of genes associated with lipid metabolism. Altogether, our data indicate that RXR activation is beneficial to preclinical models of DR.
摘要：
以前,RXR激动剂UAB126通过控制血糖水平(BGL)和改变与脂质代谢和炎症反应相关的基因表达,证明其治疗肥胖小鼠的潜在治疗价值.该研究的目的是评估UAB126对1型糖尿病（T1D）啮齿动物模型中糖尿病视网膜病变（DR）进展的影响，链脲佐菌素诱导，和2型糖尿病（T2D），在db/db小鼠中。UAB126治疗通过口服灌胃6周或通过局部施用滴眼剂2周递送。在治疗结束时,通过视网膜电图（ERG）评估糖尿病小鼠的视网膜功能，并收集他们的视网膜组织进行蛋白质和基因表达分析。分离骨髓细胞并分化成骨髓来源的巨噬细胞(BMDM)。进行糖酵解应激测试和2-DG葡萄糖摄取分析。我们的结果表明，在UAB126治疗的糖尿病BMDMs中，与未治疗的糖尿病BMDMs相比，ECAR速率和2-DG摄取得到改善。在UAB126治疗的糖尿病小鼠中，高血糖减少,并与ERG振幅的保留和AMPK活性增强相关.用局部UAB126治疗的糖尿病小鼠的视网膜显示Rxr和Ppar以及与脂质代谢相关的基因表达增加。总之,我们的数据表明RXR激活对DR的临床前模型有益.
