University Eye Clinic Maastricht, Maastricht University Medical Center+ (MUMC+), 6202 AZ, Maastricht, the Netherlands; School for Mental Health and Neuroscience, Maastricht University, 6229 ER, Maastricht, the Netherlands; Chemelot Institute for Science and Technology (InSciTe), 6229 GS, Maastricht, the Netherlands.
University Eye Clinic Maastricht, Maastricht University Medical Center+ (MUMC+), 6202 AZ, Maastricht, the Netherlands; School for Mental Health and Neuroscience, Maastricht University, 6229 ER, Maastricht, the Netherlands; Chemelot Institute for Science and Technology (InSciTe), 6229 GS, Maastricht, the Netherlands.
Exp Eye Res. 2022 Apr;217:108972. doi: 10.1016/j.exer.2022.108972. Epub 2022 Jan 31.
Glaucoma, a degenerative disease of the optic nerve, is the leading cause of irreversible blindness worldwide. Currently, there is no curative treatment. The only proven treatment is lowering intraocular pressure (IOP), the most important risk factor. Glaucoma filtration surgery (GFS) can effectively lower IOP. However, approximately 10% of all surgeries fail yearly due to excessive wound healing, leading to fibrosis. GFS animal models are commonly used for the development of novel treatment modalities. The aim of the present review was to provide an overview of available animal models and anti-fibrotic drug candidates. MEDLINE and Embase were systematically searched. Manuscripts until September 1st 2021 were included. Studies that used animal models of GFS were included in this review. Additionally, the snowball method was used to identify other publications which had not been identified through the systematic search. Two hundred articles were included in this manuscript. Small rodents (e.g. mice and rats) are often used to study the fibrotic response after GFS and to test drug candidates. Due to their larger eyes, rabbits are better suited to develop medical devices. Novel drugs aim to inhibit specific pathways, e.g. through the use of modulators, monoclonal antibodies, aqueous suppressants or gene therapy. Although most newly studied drugs offer a higher safety profile compared to antimetabolites, their efficacy is in most cases lower when compared to MMC. Current literature on animal models and potential drug candidates for GFS were summarized in this review. Future research should focus on refining current animal models (for example through the induction of glaucoma prior to undertaking GFS) and standardizing animal research to ensure a higher reproducibility and reliability across different research groups. Lastly, novel therapies need to be further optimized, e.g. by conducting more research on the dosage, administration route, application frequency, the option of creating combination therapies, or the development of drug delivery systems for sustained release of anti-fibrotic medication.
青光眼是一种视神经退行性疾病，是全球导致不可逆性失明的主要原因。目前尚无有效的治疗方法。唯一被证实的治疗方法是降低眼内压（IOP），这是最重要的危险因素。青光眼滤过手术（GFS）可以有效地降低眼压。然而，每年约有 10%的手术因过度伤口愈合而失败，导致纤维化。GFS 动物模型常用于开发新的治疗方法。本综述的目的是提供可用的动物模型和抗纤维化药物候选物的概述。系统地检索了 MEDLINE 和 Embase。纳入截至 2021 年 9 月 1 日的文献。本综述纳入了使用 GFS 动物模型的研究。此外，还使用雪球法确定了其他未通过系统搜索发现的出版物。本文共纳入 200 篇文章。小型啮齿动物（如小鼠和大鼠）常用于研究 GFS 后纤维化反应，并测试药物候选物。由于兔子的眼睛较大，它们更适合开发医疗器械。新型药物旨在抑制特定途径，例如使用调节剂、单克隆抗体、水性抑制剂或基因治疗。虽然与抗代谢物相比，大多数新研究的药物具有更高的安全性，但与 MMC 相比，它们的疗效在大多数情况下较低。本文综述了 GFS 的动物模型和潜在药物候选物的最新研究进展。未来的研究应集中在改进当前的动物模型（例如，在进行 GFS 之前诱导青光眼）和标准化动物研究，以确保不同研究小组之间具有更高的重现性和可靠性。最后，需要进一步优化新型疗法，例如通过进一步研究剂量、给药途径、应用频率、创建联合疗法的选择，或开发用于持续释放抗纤维化药物的药物输送系统。
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