Purpose of Review

Diabetic retinopathy (DR), a leading cause of visual impairment in the developed country, is characterized by vascular lesions and neuronal damage of the retina. Treatment options for this condition are currently limited. The advent of therapy targeting vascular endothelial growth factor (VEGF) demonstrated significant benefits to patients with DR. However, this treatment is limited by its short half-life and requirement for frequent invasive intravitreal injections. In addition, many patients failed to achieve clinically significant improvement in visual function. Gene therapy has the potential to provide an alternative treatment for DR with distinct advantages, such as longer therapeutic effect, less injection frequency, ability to intervene at disease onset, and potentially fewer side effects.

Recent Findings

Strategies for gene therapy in DR, stemming from the current understanding of the disease pathogenesis, focus on the inhibition of neovascularization and protection of neurovascular degeneration in the retina. Studies with promising results have mainly focussed on animal models due to efficacy and safety concerns, despite a number of successful preclinical studies using adeno-associated virus-mediated transduction to treat both vascular dysfunction and neuronal degeneration. With the optimization of delivery vectors, transgene regulation, and outcome measure, gene therapy will potentially become available for patients with DR.

Summary

This review provides an update on the current strategies utilized in DR gene therapy research. Several barriers to the clinical application of gene therapy for DR are highlighted, and future directions for this research are proposed.

中文翻译：

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糖尿病视网膜病变基因治疗的最新进展。

审查目的

糖尿病性视网膜病（DR）是发达国家视力障碍的主要原因，其特征在于血管病变和视网膜神经元损害。目前，针对这种情况的治疗选择有限。靶向血管内皮生长因子（VEGF）的治疗方法的出现为DR患者带来了显着益处。但是，这种治疗方法的半衰期短，需要频繁地侵入玻璃体内注射。另外，许多患者未能实现视觉功能的临床显着改善。基因治疗具有为DR提供替代治疗的潜力，具有明显的优势，例如更长的治疗效果，更少的注射频率，在疾病发作时进行干预的能力以及潜在的更少的副作用。

最近的发现

从目前对疾病发病机理的了解出发，DR的基因治疗策略着重于抑制新生血管形成和保护视网膜神经血管变性。尽管有许多成功的临床前研究使用腺相关病毒介导的转导来治疗血管功能障碍和神经元变性，但由于疗效和安全性问题，具有良好结果的研究主要集中在动物模型上。随着递送载体，转基因调节和结果测量的优化，DR的患者有可能获得基因治疗。

概要

这篇评论提供了DR基因疗法研究中使用的当前策略的更新。突显了DR基因治疗在临床上的一些障碍，并提出了该研究的未来方向。