Gene Therapy Reduces Eye Pressure in Mice, Offers Potential Alternative to Glaucoma Drops

基因疗法降低小鼠眼压，提供青光眼滴剂的潜在替代方案

June 18, 2025

2025年6月18日

A new study suggests gene editing could offer a reversible and less frequent alternative to daily eye drops for glaucoma, one of the world’s leading causes of irreversible blindness. The findings, published in PNAS Nexus, point to a promising therapeutic approach for managing intraocular pressure (IOP)..

一项新的研究表明，基因编辑可能提供一种可逆且比每日使用眼药水频率更低的替代方案，用于治疗青光眼，这是全球不可逆失明的主要原因之一。发表在《PNAS Nexus》上的研究结果指出了管理眼内压（IOP）的一种有前景的治疗方法。

Current Limitations of Glaucoma Treatment

青光眼治疗的当前局限性

Glaucoma patients typically rely on daily eye drops to manage elevated eye pressure. However, these treatments often come with complications, including:

青光眼患者通常依靠每日使用眼药水来控制眼压升高。然而，这些治疗常常伴随着并发症，包括：

• Bradycardia

• 心动过缓

• Metabolic acidosis

代谢性酸中毒

• Kidney stones

• 肾结石

Moreover, patient noncompliance with daily regimens poses a significant challenge in long-term disease management.

此外，患者对日常治疗方案的不依从性在长期疾病管理中构成了重大挑战。

Targeted Gene Editing with CRISPR Cas13d

使用CRISPR Cas13d进行靶向基因编辑

In the study, Yang Sun, MD, PhD, and colleagues used a CRISPR-based gene editing technique to lower IOP in mice. Specifically, the team employed Cas13d, an RNA-targeting CRISPR effector, to downregulate the mRNAs for:

在研究中，杨森医学博士及其同事使用了一种基于CRISPR的基因编辑技术来降低小鼠的眼内压。具体来说，研究团队采用了Cas13d，一种靶向RNA的CRISPR效应器，来下调以下mRNA：

• Aquaporin 1 (AQP1)

• 水通道蛋白1（AQP1）

• Carbonic anhydrase type 2 (CA2)

• 碳酸酐酶2型（CA2）

These genes are involved in the production of aqueous humor in the eye. The editing was localized to the ciliary body, the eye structure responsible for fluid production.

这些基因参与了眼睛内房水的产生。编辑工作集中在睫状体，这是负责液体产生的结构。

Significant and Reversible IOP Reduction

显著且可逆的眼压降低

Cas13d-treated mice exhibited significantly lower intraocular pressure compared to untreated controls across both wild-type and glaucoma mouse models. Importantly, the therapy does not permanently alter DNA, making the effects reversible and adjustable—a key advantage over conventional gene editing strategies..

Cas13d处理的小鼠在野生型和青光眼小鼠模型中，眼内压均显著低于未处理的对照组。重要的是，这种疗法不会永久改变DNA，使得其效果可逆且可调节——这是相较于传统基因编辑策略的一大优势。

Path to Clinical Translation

临床转化路径

While the results are promising, the authors caution that additional steps are required before this approach can be applied to humans. These include:

虽然结果令人鼓舞，但作者警告说，在这种方法应用于人类之前，还需要采取一些额外的步骤。这些步骤包括：

• Optimizing timing and dosage

• 优化时机和剂量

• Developing a noninvasive delivery method

• 开发一种非侵入性的递送方法

• Establishing safety and efficacy in human trials

• 在人体试验中确立安全性和有效性

The authors note that this gene therapy may only need to be administered monthly or even less frequently, making it a potentially transformative solution for millions of glaucoma patients worldwide.

作者指出，这种基因疗法可能只需每月甚至更少频率给药一次，从而为全球数百万青光眼患者提供了一种潜在的变革性解决方案。

Reference:

参考：

Siyu Chen et al. Gene therapy for ocular hypertension using hfCas13d-mediated mRNA targeting, PNAS Nexus (2025). DOI: 10.1093/pnasnexus/pgaf168.

陈思宇等。使用hfCas13d介导的mRNA靶向治疗眼压升高的基因疗法，《PNAS Nexus》（2025）。DOI: 10.1093/pnasnexus/pgaf168。