Bolinger Mark T, Antonetti David A
Departments of Ophthalmology and Visual Sciences, Kellogg Eye Center, and Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48105, USA.
Int J Mol Sci. 2016 Sep 7;17(9):1498. doi: 10.3390/ijms17091498.
Diabetic retinopathy is the leading cause of blindness in working age adults, and is projected to be a significant future health concern due to the rising incidence of diabetes. The recent advent of anti-vascular endothelial growth factor (VEGF) antibodies has revolutionized the treatment of diabetic retinopathy but a significant subset of patients fail to respond to treatment. Accumulating evidence indicates that inflammatory cytokines and chemokines other than VEGF may contribute to the disease process. The current review examines the presence of non-VEGF cytokines in the eyes of patients with diabetic retinopathy and highlights mechanistic pathways in relevant animal models. Finally, novel drug targets including components of the kinin-kallikrein system and emerging treatments such as anti-HPTP (human protein tyrosine phosphatase) β antibodies are discussed. Recognition of non-VEGF contributions to disease pathogenesis may lead to novel therapeutics to enhance existing treatments for patients who do not respond to anti-VEGF therapies.
糖尿病性视网膜病变是工作年龄成年人失明的主要原因，并且由于糖尿病发病率的上升，预计将成为未来一个重大的健康问题。抗血管内皮生长因子（VEGF）抗体的近期出现彻底改变了糖尿病性视网膜病变的治疗方法，但有相当一部分患者对治疗无反应。越来越多的证据表明，除VEGF外，炎性细胞因子和趋化因子可能也参与了疾病的发生发展过程。本综述研究了糖尿病性视网膜病变患者眼中非VEGF细胞因子的存在情况，并着重介绍了相关动物模型中的作用机制途径。最后，讨论了包括激肽-激肽释放酶系统成分在内的新型药物靶点以及诸如抗人蛋白酪氨酸磷酸酶（HPTP）β抗体等新兴治疗方法。认识到非VEGF在疾病发病机制中的作用可能会带来新的治疗方法，以加强对那些对抗VEGF治疗无反应的患者的现有治疗。
