Department of Ophthalmology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiaotong University, No.100 Haining Road, Shanghai, 200080, China.
Graefes Arch Clin Exp Ophthalmol. 2015 May;253(5):669-80. doi: 10.1007/s00417-015-2985-3. Epub 2015 Mar 20.
Diabetic retinopathy (DR) is a major cause of blindness in the working-age populations of developed countries, and effective treatments and prevention measures have long been the foci of study. Patients with DR invariably demonstrate impairments of the retinal microvascular endothelium. Many observational and preclinical studies have shown that angiogenesis and apoptosis play crucial roles in the pathogenesis of DR. Increasing evidence suggests that in DR, the small guanosine-5'-triphosphate-binding protein RhoA activates its downstream targets mammalian Diaphanous homolog 1 (mDia-1) and profilin-1, thus affecting important cellular functions, including cell morphology, motility, secretion, proliferation, and gene expression. However, the specific underlying mechanism of disease remains unclear.
This review focuses on the RhoA/mDia-1/profilin-1 signaling pathway that specifically triggers endothelial dysfunction in diabetic patients. Recently, RhoA and profilin-1 signaling has attracted a great deal of attention in the context of diabetes-related research. However, the precise molecular mechanism by which the RhoA/mDia-1/profilin-1 pathway is involved in progression of microvascular endothelial dysfunction (MVED) during DR has not been determined. This review briefly describes each feature of the cascade before exploring the most recent findings on how the pathway may trigger endothelial dysfunction in DR. When the underlying mechanisms are understood, novel therapies seeking to restore the endothelial homeostasis comprised in DR will become possible.
糖尿病视网膜病变（DR）是发达国家工作年龄段人群失明的主要原因，长期以来，有效的治疗和预防措施一直是研究的重点。DR 患者的视网膜微血管内皮细胞必然受损。许多观察性和临床前研究表明，血管生成和细胞凋亡在 DR 的发病机制中起关键作用。越来越多的证据表明，在 DR 中，小分子鸟苷三磷酸结合蛋白 RhoA 激活其下游靶蛋白哺乳动物 Dia 同源物 1（mDia-1）和丝氨酸羟甲基转移酶，从而影响重要的细胞功能，包括细胞形态、运动、分泌、增殖和基因表达。然而，疾病的确切潜在机制仍不清楚。
本文重点介绍了 RhoA/mDia-1/丝氨酸羟甲基转移酶信号通路，该通路特异性触发糖尿病患者的内皮功能障碍。最近，RhoA 和丝氨酸羟甲基转移酶信号在与糖尿病相关的研究中引起了极大的关注。然而，RhoA/mDia-1/丝氨酸羟甲基转移酶通路在 DR 中小血管内皮功能障碍（MVED）进展中的确切分子机制尚未确定。本文简要描述了级联反应的每个特征，然后探讨了该通路如何引发 DR 中内皮功能障碍的最新发现。当了解了潜在的机制，就有可能找到恢复 DR 中内皮稳态的新疗法。
