Systemic TRPV4 inhibition worsens retinal response to acute intraocular pressure elevation in older but not younger mice.

IF 1.6 4区医学 Q3 OPHTHALMOLOGY

Optometry and Vision Science Pub Date : 2025-02-01 Epub Date: 2025-01-30 DOI:10.1097/OPX.0000000000002217

Pei Ying Lee, Ursula Greferath, Da Zhao, Jin Y Huang, Anna Y M Wang, Kirstan A Vessey, Vicki Chrysostomou, Erica L Fletcher, Jonathan G Crowston, Bang V Bui

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引用次数: 0

Abstract

Significance: Previous evidence showed that transient receptor potential vanilloid 4 (TRPV4) inhibition was protective of retinal ganglion cell (RGC) loss after chronic intraocular pressure (IOP) elevation in young animals. However, the role of TRPV4 in mechanosensing IOP changes in the aging eye is not well understood.

Purpose: This study compared the recovery of retinal function and structure after acute IOP elevation in 3- and 12-month-old mouse eyes with and without TRPV4 inhibition.

Methods: We examined retinal TRPV4 expression in 2-month-old rodent eyes using immunohistochemistry and transcript analysis of isolated macroglia and RGCs. To modulate TRPV4, mice were treated daily with either vehicle or a TRPV4 antagonist (HC-067047 10 mg/kg) delivered intraperitoneally for 7 days before and 7 days after IOP elevation (50 mmHg for 30 minutes). Retinal function and structure were assessed using dark-adapted full-field electroretinography and optical coherence tomography, respectively.

Results: We showed that Müller cells strongly expressed TRPV4. Seven days after IOP elevation, RGC functional recovery was significantly poorer in older mice treated with TRPV4 antagonist compared with age-matched vehicle controls (-54 ± 7% vs. -24 ± 10%, p=0.046) and their younger TRPV4 antagonist-treated counterparts (-5 ± 5%, p<0.001).

Conclusions: This study showed that there was an age-related deficit in RGC functional recovery from IOP elevation with TRPV4 inhibition.

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全身性TRPV4抑制会使老年小鼠的视网膜对急性眼压升高的反应恶化，而非年轻小鼠。

意义：已有证据表明，抑制瞬时受体电位香草样蛋白4 （TRPV4）对幼龄动物慢性眼压升高后视网膜神经节细胞（RGC）丢失具有保护作用。然而，TRPV4在老化眼机械感测IOP变化中的作用尚不清楚。目的：本研究比较了3月龄和12月龄小鼠急性IOP升高后视网膜功能和结构的恢复情况。方法：采用免疫组化和分离的大胶质细胞和RGCs转录分析方法检测2月龄鼠眼视网膜TRPV4的表达。为了调节TRPV4，小鼠在IOP升高前7天和IOP升高后7天（50 mmHg， 30分钟）每天腹腔注射载体或TRPV4拮抗剂（HC-067047 10 mg/kg）。分别使用适应黑暗的全视场视网膜电图和光学相干断层扫描评估视网膜功能和结构。结果：我们发现m ller细胞强烈表达TRPV4。IOP升高后7天，与年龄匹配的对照相比，使用TRPV4拮抗剂治疗的老年小鼠RGC功能恢复明显较差（-54±7% vs -24±10%,p=0.046），与使用TRPV4拮抗剂治疗的年轻小鼠相比（-5±5%,p）。结论：本研究表明，使用TRPV4拮抗剂治疗的IOP升高后RGC功能恢复存在年龄相关缺陷。

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

Optometry and Vision Science 医学-眼科学

CiteScore

2.80

自引率

7.10%

发文量

210

审稿时长

3-6 weeks

期刊介绍： Optometry and Vision Science is the monthly peer-reviewed scientific publication of the American Academy of Optometry, publishing original research since 1924. Optometry and Vision Science is an internationally recognized source for education and information on current discoveries in optometry, physiological optics, vision science, and related fields. The journal considers original contributions that advance clinical practice, vision science, and public health. Authors should remember that the journal reaches readers worldwide and their submissions should be relevant and of interest to a broad audience. Topical priorities include, but are not limited to: clinical and laboratory research, evidence-based reviews, contact lenses, ocular growth and refractive error development, eye movements, visual function and perception, biology of the eye and ocular disease, epidemiology and public health, biomedical optics and instrumentation, novel and important clinical observations and treatments, and optometric education.