Identification of novel drug targets for the treatment of diabetic retinopathy.
Identification of novel drug targets for the treatment of diabetic retinopathy.
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DOI：
10.4093/dmj.2013.37.4.217
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发表时间：
2013-08
影响因子：
5.9
通讯作者：
Uemura A
中科院分区：
文献类型：
--
作者：
Uemura A
糖尿病视网膜病变（DR）的视力丧失可归因于导致黄斑水肿和新生血管形成的视网膜血管病症。除了激光光凝疗法，眼内注射抗血管内皮生长因子药物也有助于治疗这些疾病。尽管如此，眼内给药的临床可行性提出了越来越多的需求，以开发替代药物，可以从根本上改善视网膜血管功能障碍的DR。为此，实验动物模型，重现人类DR将是临床上的好处。尽管在大鼠或小鼠中不能获得DR模型，但无高血糖症的药理学和遗传操作已成功地重现了出生后小鼠视网膜中的视网膜水肿和新生血管生成，本文重点介绍了视网膜血管异常的实验小鼠模型的实用性，并讨论了DR发病和进展的细胞和分子机制。这些方法将导致识别新的药物靶点，用于恢复DR中血管完整性和功能性毛细血管再生。
Vision loss in diabetic retinopathy (DR) is attributable to retinal vascular disorders that result in macular edema and neoangiogenesis. In addition to laser photocoagulation therapy, intraocular injections of antivascular endothelial growth factor drugs have contributed to the treatment of these disease conditions. Nonetheless, the clinical feasibility of intraocular drug administration has raised an increasing demand to develop alternative drugs that can fundamentally ameliorate the retinal vascular dysfunctions in DR. For this purpose, experimental animal models that reproduce human DR would be of clinical benefit. Despite the unavailability of DR models in rats or mice, pharmacological and genetic manipulations without hyperglycemia have successfully recapitulated retinal edema and neoangiogenesis in postnatal mouse retinas, thereby enabling the understanding of the pathophysiology underlying DR. This article highlights the utility of experimental mouse models of retinal vascular abnormalities and discusses cellular and molecular mechanisms responsible for the onset and progression of DR. These approaches will lead to the identification of novel drug targets for the restoration of vascular integrity and regeneration of functional capillaries in DR.