Behl Tapan, Velpandian Thirumurthy, Kotwani Anita
Department of Pharmacology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, India.
Department of Ocular Pharmacology, Dr. Rajendra Prasad Centre for Ophthalmic Science, AIIMS, New Delhi, India.
Vascul Pharmacol. 2017 May;92:1-5. doi: 10.1016/j.vph.2017.03.005. Epub 2017 Mar 31.
The implications of altered coagulation-fibrinolytic system in the pathophysiology of several vascular disorders, such as stroke and myocardial infarction, have been well researched upon and established. However, its role in the progression of diabetic retinopathy has not been explored much. Since a decade, it is known that hyperglycemia is associated with a hypercoagulated state and the various impairments it causes are well acknowledged as independent risk factors for the development of cardiovascular diseases. But recent studies suggest that the hypercoagulative state and diminished fibrinolytic responses might also alter retinal homeostasis and induce several deleterious molecular changes in retinal cells which aggravate the already existing hyperglycemia-induced pathological conditions and thereby lead to the progression of diabetic retinopathy. The major mediators of coagulation-fibrinolytic system whose concentration or activity get altered during hyperglycemia include fibrinogen, antithrombin-III (AT-III), plasminogen activator inhibitor-1 (PAI-1) and von Willebrand factor (vWF). Inhibiting the pathways by which these altered mediators get involved in the pathophysiology of diabetic retinopathy can serve as potential targets for the development of an adjuvant novel alternative therapy for diabetic retinopathy.
凝血-纤溶系统的改变在几种血管疾病(如中风和心肌梗死)的病理生理学中的影响已得到充分研究和证实。然而,其在糖尿病视网膜病变进展中的作用尚未得到充分探索。十年来,人们已经知道高血糖与高凝状态有关,并且它所导致的各种损害被公认为是心血管疾病发展的独立危险因素。但最近的研究表明,高凝状态和纤溶反应减弱也可能改变视网膜内环境稳态,并在视网膜细胞中诱导几种有害的分子变化,这些变化会加重已有的高血糖诱导的病理状况,从而导致糖尿病视网膜病变的进展。在高血糖期间其浓度或活性发生改变的凝血-纤溶系统的主要介质包括纤维蛋白原、抗凝血酶III(AT-III)、纤溶酶原激活物抑制剂-1(PAI-1)和血管性血友病因子(vWF)。抑制这些改变的介质参与糖尿病视网膜病变病理生理学的途径,可以作为开发糖尿病视网膜病变辅助新型替代疗法的潜在靶点。