Investigation into the usefulness of cynomolgus monkeys with spontaneously elevated intraocular pressure as a model for glaucoma treatment research

IF 3 3区 医学 Q2 PHARMACOLOGY & PHARMACY Journal of pharmacological sciences Pub Date : 2023-12-17 DOI:10.1016/j.jphs.2023.12.004
Tomoaki Araki , Masamitsu Shimazawa , Shinsuke Nakamura , Wataru Otsu , Yosuke Numata , Megumi Sakata , Koji Kabayama , Hideshi Tsusaki , Hideaki Hara
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Abstract

Many glaucoma treatments focus on lowering intraocular pressure (IOP), with novel drugs continuing to be developed. One widely used model involves raising IOP by applying a laser to the trabecular iris angle (TIA) of cynomolgus monkeys to damage the trabecular meshwork. This model, however, presents challenges such as varying IOP values, potential trabecular meshwork damage, and risk of animal distress. This study investigated whether animals with naturally high IOP (>25 mmHg) could be used to effectively evaluate IOP-lowering drugs, thereby possibly replacing laser-induced models. Relationships between TIA size, IOP, and pupil diameter were also examined. Three representative IOP-lowering drugs (latanoprost, timolol, ripasudil) were administered, followed by multiple IOP measurements and assessment of corneal thickness, TIA, and pupil diameter via anterior segment optical coherence tomography (AS-OCT). There was a positive correlation was noted between IOP and corneal thickness before instillation, and a negative correlation between IOP and TIA before instillation. Our findings suggest animals with naturally high IOP could be beneficial for glaucoma research and development as a viable replacement for the laser-induced model and that measuring TIA using AS-OCT along with IOP yields a more detailed evaluation.

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将自发性眼压升高的猕猴作为青光眼治疗模型的实用性研究
许多青光眼治疗方法都侧重于降低眼压(IOP),新型药物也在不断开发中。一种被广泛使用的模型是通过在猴子的小梁虹膜角(TIA)上使用激光来提高眼压,从而破坏小梁网。然而,这种模型也存在一些挑战,如不同的眼压值、潜在的小梁网损伤以及动物痛苦的风险。本研究调查了自然高眼压(25 mmHg)动物是否可用于有效评估降眼压药物,从而可能取代激光诱导模型。研究还考察了TIA大小、眼压和瞳孔直径之间的关系。在使用三种具有代表性的降眼压药物(拉坦前列素、噻吗洛尔、利帕舒地尔)后,通过前节光学相干断层扫描(AS-OCT)测量了多次眼压并评估了角膜厚度、TIA 和瞳孔直径。灌药前的眼压与角膜厚度呈正相关,灌药前的眼压与TIA呈负相关。我们的研究结果表明,天然高眼压动物可作为激光诱导模型的可行替代品,有益于青光眼的研究和开发,而且使用 AS-OCT 测量 TIA 和眼压可获得更详细的评估。
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来源期刊
CiteScore
6.20
自引率
2.90%
发文量
104
审稿时长
31 days
期刊介绍: Journal of Pharmacological Sciences (JPS) is an international open access journal intended for the advancement of pharmacological sciences in the world. The Journal welcomes submissions in all fields of experimental and clinical pharmacology, including neuroscience, and biochemical, cellular, and molecular pharmacology for publication as Reviews, Full Papers or Short Communications. Short Communications are short research article intended to provide novel and exciting pharmacological findings. Manuscripts concerning descriptive case reports, pharmacokinetic and pharmacodynamic studies without pharmacological mechanism and dose-response determinations are not acceptable and will be rejected without peer review. The ethnopharmacological studies are also out of the scope of this journal. Furthermore, JPS does not publish work on the actions of biological extracts unknown chemical composition.
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