Tajnšek Špela, Petrovič Danijel, Globočnik Petrovič Mojca, Kunej Tanja
University of Ljubljana, Biotechnical Faculty, Department of Animal Science, Slovenia.
University of Ljubljana, Faculty of Medicine, Institute of Histology and Embryology, Slovenia.
PPAR Res. 2020 Mar 3;2020:1783564. doi: 10.1155/2020/1783564. eCollection 2020.
Diabetic retinopathy (DR) is a condition that develops after long-lasting and poorly handled diabetes and is presently the main reason for blindness among elderly and youth. Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that are involved in carbohydrate and fatty-acid metabolism and have also been associated with DR. Three PPAR isoforms are known: , , and . In the present study, we retrieved articles reporting associations between PPARs and DR from PubMed database and compiled the data in two catalogues, for human and animal models. Extracted data was then complemented with additional relevant genomic information. Seven retrieved articles reported testing an association between with DR in human. Four of them concluded association of and with DR in European and Asian populations, having a protective role on DR development. One study reported pathogenic role of , while two articles reported no association between and DR among Indian and Chinese populations. Six retrieved articles reported testing of involvement of and in DR in animal models, including mouse and rat. The review includes case-control studies, meta-analysis, expression studies, animal models, and cell line studies. Despite a large number of documented sequence variants of the PPAR genes available in genome browsers, researchers usually focus on a small set of previously reported variants. Data extraction from Ensembl genome browser revealed several sequence variants with predicted deleterious effect on protein function which present candidates for further experimental validation. Results of the present analysis will enable more holistic approach for understanding of in DR development. Additionally, developed catalogues present a baseline for standardized reporting of PPAR-phenotype association in upcoming studies.
糖尿病视网膜病变（DR）是一种在长期糖尿病控制不佳后出现的病症，目前是老年人和年轻人失明的主要原因。过氧化物酶体增殖物激活受体（PPARs）是参与碳水化合物和脂肪酸代谢的核受体，也与糖尿病视网膜病变有关。已知有三种PPAR亚型： 、 和 。在本研究中，我们从PubMed数据库中检索了报告PPARs与DR之间关联的文章，并将数据整理成两个人和动物模型的目录。然后，提取的数据用其他相关的基因组信息进行补充。七篇检索到的文章报告了在人类中测试 与DR之间的关联。其中四篇得出结论，在欧洲和亚洲人群中， 和 与DR有关联，对DR的发展具有保护作用。一项研究报告了 的致病作用，而两篇文章报告在印度和中国人群中 与DR之间无关联。六篇检索到的文章报告了在动物模型（包括小鼠和大鼠）中测试 和 与DR的相关性。该综述包括病例对照研究、荟萃分析、表达研究、动物模型和细胞系研究。尽管基因组浏览器中有大量记录的PPAR基因序列变异，但研究人员通常关注一小部分先前报道的变异。从Ensembl基因组浏览器中提取的数据揭示了几个对蛋白质功能有预测有害影响的序列变异，这些变异是进一步实验验证的候选对象。本分析的结果将有助于更全面地理解 在DR发展中的作用。此外，编制的目录为即将开展的研究中PPAR-表型关联的标准化报告提供了基线。
