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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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.