P2X4 Receptor Antagonist Ameliorates Ocular Pain in Rats After Lacrimal Gland Removal.

IF 2.6 3区医学 Q2 OPHTHALMOLOGY

Translational Vision Science & Technology Pub Date : 2025-09-02 DOI:10.1167/tvst.14.9.11

Minjie Chen, Stefan Bäurle, Marcus Karlstetter, Xianni Simmons, Stefanie Seo, Samuel C Yiu

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引用次数: 0

Abstract

Purpose: The purinergic receptor P2X4 is critical to transduction of ocular pain. The aim of this study was to investigate the therapeutic potential of the P2X4 receptor antagonist BAY-776 in alleviating chronic ocular pain.

Methods: Chronic ocular pain was induced in male rats (8-9 weeks old; n = 12 per group) via double lacrimal gland removal (DLGR). Rats were randomly assigned to receive vehicle control, 1.0 mg/mL BAY-776, or 2.5 mg/mL BAY-776 eyedrops after DLGR. Treatment efficacy was assessed with blink tests, wipe tests, and in vivo confocal microscopy (IVCM) at pre- and postsurgical baselines and 2 and 4 weeks of treatment. Corneal subbasal nerve plexus (SNP) density and inflammatory cells were quantified by IVCM image analysis and immunohistochemical staining. Efficacies of 2.5 mg/mL BAY-776 and 0.05% cyclosporine were also compared.

Results: Compared with vehicle control, BAY-776 at both concentrations significantly reduced wipe and blink responses (P < 0.01). BAY-776 mitigated the increases in corneal SNP and inflammatory cell density after DLGR (P < 0.01). Notably, BAY-776 at 2.5 mg/mL reduced wipe test scores and inflammatory cell density at levels comparable to those of 0.05% cyclosporine (P < 0.001). Although cyclosporine did not significantly affect the blink test compared with vehicle, it reduced SNP density compared with BAY-776 (P < 0.05).

Conclusions: The results indicate that BAY-776 effectively reduced chronic ocular pain in rats, showing efficacy similar to that of cyclosporine and underscoring its therapeutic potential for managing ocular pain.

Translational relevance: These results suggest that BAY-776 may be a promising option for managing chronic ocular pain.

Abstract Image

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P2X4受体拮抗剂改善大鼠泪腺切除后的眼痛。

目的：嘌呤能受体P2X4在眼痛的转导过程中起关键作用。本研究的目的是探讨P2X4受体拮抗剂BAY-776在缓解慢性眼痛方面的治疗潜力。方法：雄性大鼠（8-9周龄，每组12只）采用双泪腺摘除法（DLGR）诱导慢性眼痛。大鼠在DLGR后随机接受载体对照、1.0 mg/mL BAY-776滴眼液和2.5 mg/mL BAY-776滴眼液。在术前和术后基线以及治疗2周和4周时，通过眨眼试验、擦拭试验和体内共聚焦显微镜（IVCM）评估治疗效果。采用IVCM图像分析和免疫组化染色定量检测角膜基底下神经丛（SNP）密度和炎症细胞。还比较了2.5 mg/mL BAY-776和0.05%环孢素的效果。结果：与对照相比，两种浓度的BAY-776均显著降低了小鼠的擦眼和眨眼反应（P < 0.01）。BAY-776可减轻DLGR后角膜SNP和炎症细胞密度的升高（P < 0.01）。值得注意的是，与0.05%环孢素相比，2.5 mg/mL的BAY-776可降低擦拭测试分数和炎症细胞密度（P < 0.001）。与对照相比，环孢素对眨眼试验的影响不显著，但与BAY-776相比，环孢素降低了SNP密度（P < 0.05）。结论：结果表明BAY-776能有效减轻大鼠慢性眼痛，其疗效与环孢素相似，强调了其治疗眼痛的潜力。翻译相关性：这些结果表明BAY-776可能是治疗慢性眼痛的一个有希望的选择。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Translational Vision Science & Technology Engineering-Biomedical Engineering

CiteScore

5.70

自引率

3.30%

发文量

346

审稿时长

25 weeks

期刊介绍： Translational Vision Science & Technology (TVST), an official journal of the Association for Research in Vision and Ophthalmology (ARVO), an international organization whose purpose is to advance research worldwide into understanding the visual system and preventing, treating and curing its disorders, is an online, open access, peer-reviewed journal emphasizing multidisciplinary research that bridges the gap between basic research and clinical care. A highly qualified and diverse group of Associate Editors and Editorial Board Members is led by Editor-in-Chief Marco Zarbin, MD, PhD, FARVO. The journal covers a broad spectrum of work, including but not limited to: Applications of stem cell technology for regenerative medicine, Development of new animal models of human diseases, Tissue bioengineering, Chemical engineering to improve virus-based gene delivery, Nanotechnology for drug delivery, Design and synthesis of artificial extracellular matrices, Development of a true microsurgical operating environment, Refining data analysis algorithms to improve in vivo imaging technology, Results of Phase 1 clinical trials, Reverse translational ("bedside to bench") research. TVST seeks manuscripts from scientists and clinicians with diverse backgrounds ranging from basic chemistry to ophthalmic surgery that will advance or change the way we understand and/or treat vision-threatening diseases. TVST encourages the use of color, multimedia, hyperlinks, program code and other digital enhancements.