Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia; Ophthalmology, Department of Surgery, University of Melbourne, Melbourne, Victoria, Australia.
Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia; Discipline of Ophthalmology, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
Pharmacol Ther. 2017 May;173:1-18. doi: 10.1016/j.pharmthera.2017.01.003. Epub 2017 Jan 27.
Diabetic retinopathy (DR), a chronic and progressive complication of diabetes mellitus, is a sight-threatening disease characterized in the early stages by neuronal and vascular dysfunction in the retina, and later by neovascularization that further damages vision. A major contributor to the pathology is excess production of vascular endothelial growth factor (VEGF), a growth factor that induces formation of new blood vessels and increases permeability of existing vessels. Despite the recent availability of effective treatments for the disease, including laser photocoagulation and therapeutic VEGF antibodies, DR remains a significant cause of vision loss worldwide. Existing anti-VEGF agents, though generally effective, are limited by their short therapeutic half-lives, necessitating frequent intravitreal injections and the risk of attendant adverse events. Management of DR with gene therapies has been proposed for several years, and pre-clinical studies have yielded enticing findings. Gene therapy holds several advantages over conventional treatments for DR, such as a longer duration of therapeutic effect, simpler administration, the ability to intervene at an earlier stage of the disease, and potentially fewer side-effects. In this review, we summarize the current understanding of the pathophysiology of DR and provide an overview of research into DR gene therapies. We also examine current barriers to the clinical application of gene therapy for DR and evaluate future prospects for this approach.
糖尿病性视网膜病变（DR）是糖尿病的一种慢性进行性并发症，是一种威胁视力的疾病，其特征在早期为视网膜神经元和血管功能障碍，晚期为新生血管形成，进一步损害视力。病理的一个主要促成因素是血管内皮生长因子（VEGF）的过度产生，VEGF 是一种生长因子，可诱导新血管形成并增加现有血管的通透性。尽管最近有针对该疾病的有效治疗方法，包括激光光凝和治疗性 VEGF 抗体，但 DR 仍然是全球视力丧失的主要原因。现有的抗 VEGF 药物虽然通常有效，但由于其治疗半衰期短，需要频繁进行玻璃体内注射，并且存在伴随的不良事件风险，因此受到限制。几年来，人们一直提议使用基因疗法来治疗 DR，并且临床前研究取得了诱人的结果。基因疗法相对于 DR 的传统治疗方法具有几个优势，例如治疗效果的持续时间更长、给药更简单、能够在疾病的早期阶段进行干预，并且潜在的副作用更少。在这篇综述中，我们总结了对 DR 病理生理学的现有理解，并概述了对 DR 基因疗法的研究。我们还检查了基因疗法治疗 DR 的临床应用的当前障碍，并评估了这种方法的未来前景。
