Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, Catania, Italy.
Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, Catania, Italy; Center for Research in Ocular Pharmacology - CERFO University of Catania, Catania, Italy.
Biochem Pharmacol. 2018 Dec;158:13-26. doi: 10.1016/j.bcp.2018.09.016. Epub 2018 Sep 15.
Diabetic retinopathy was included by the World Health Organization in the eye disease priority list. Up to now, only proliferative diabetic retinopathy can be treated with approved drugs, such as intravitreal anti-vascular endothelial growth factor (VEGF) agents or steroids. In this perspective, there is the urgent need to explore novel pharmacological targets for treatment of diabetic retinopathy. Drug discovery todays exploits the noticeable ability of computational systems biology methods to identify novel drug targets in complex pathologies bearing multifactorial etiology and wide and varying symptomatology. This is especially true for diseases, where the identification of specific molecular mechanisms, and thus drug targets, is a challenging, when not impossible, task. Within this framework, we applied a systems biology approach to identify novel drug targets for diabetic retinopathy. The complexity of diabetic retinopathy was investigated through the analysis of transcriptomics data, retrieved from Gene Expression Omnibus Dataset repository (GEO) datasets. Analysis of GEO datasets was carried out with an enrichment-information approach, which gave as output a series of complex gene-pathway and drug-gene networks. Analysis of these networks identified genes and biological pathways related with inflammation, fibrosis and G protein-coupled receptors that are potentially involved in development of the disease. This analysis provided new clues on novel pharmacological targets, useful to treat diabetic retinopathy.
糖尿病视网膜病变已被世界卫生组织列入眼部疾病重点清单。到目前为止,只有增生性糖尿病视网膜病变可以用批准的药物治疗,如眼内抗血管内皮生长因子(VEGF)药物或类固醇。在这种情况下,迫切需要探索治疗糖尿病视网膜病变的新的药理学靶点。当今的药物发现利用计算系统生物学方法的显著能力,在具有多因素病因和广泛而不同的症状的复杂病理中识别新的药物靶点。对于那些识别特定分子机制(因此也是药物靶点)具有挑战性甚至不可能的疾病来说尤其如此。在这一框架内,我们应用系统生物学方法来确定糖尿病视网膜病变的新药物靶点。通过分析从基因表达综合数据库(GEO)数据集检索到的转录组学数据,研究了糖尿病视网膜病变的复杂性。使用富集信息方法对 GEO 数据集进行了分析,该方法输出了一系列复杂的基因-途径和药物-基因网络。对这些网络的分析确定了与炎症、纤维化和 G 蛋白偶联受体相关的基因和生物途径,这些基因和生物途径可能与疾病的发展有关。这项分析为治疗糖尿病视网膜病变提供了新的药理学靶点线索。