Timolol maleate, a β blocker eye drop, improved edema in a retinal vein occlusion model.

IF 1.8 3区医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Molecular Vision Pub Date : 2023-10-15 eCollection Date: 2023-01-01

Shinichiro Fuma, Yae Hidaka, Anri Nishinaka, Hiroto Yasuda, Kota Aoshima, Shinsuke Nakamura, Hideaki Hara, Masamitsu Shimazawa

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Abstract

Purpose: To investigate the therapeutic effects of eye drops, namely, timolol maleate, a β-adrenergic receptor antagonist, and latanoprost, a prostaglandin F2α analog, on retinal edema in a murine retinal vein occlusion (RVO) model.

Methods: An RVO model was established using laser-induced RVO in mice, which were administered timolol maleate and latanoprost eye drops several times after venous occlusion. Subsequently, the thickness of the inner nuclear layer (INL) and the expression levels of such genes as Vegf and Atf4, which are stress markers of the endoplasmic reticulum, were examined. Primary human cultured retinal microvascular endothelial cells (HRMECs) were treated with timolol under hypoxic conditions, after which the gene expression pattern was investigated. Importantly, an integrated stress response inhibitor (ISRIB) was used in the RVO model, he known ISRIB, which suppresses the expression of ATF4 in retinal edema.

Results: Increased INL thickness was suppressed by timolol eye drops, as were the expressions of Vegf and Atf4, in the RVO model. However, latanoprost eye drops did not induce any change in INL thickness. In HRMECs, hypoxic stress and serum deprivation increased the Vegf and Atf4 expressions; in response, treatment with timolol suppressed the Vegf expression. Furthermore, the ISRIB decreased the Vegf expression pattern and edema formation, which are associated with RVO.

Conclusions: These results indicate that timolol eye drops may be a potential option for RVO treatment.

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马来酸噻吗洛尔是一种β受体阻滞剂滴眼液，可改善视网膜静脉闭塞模型的水肿。

目的：探讨马来酸噻吗洛尔（一种β肾上腺素能受体拮抗剂）和拉坦前列素（一种前列腺素F2α类似物）滴眼液对小鼠视网膜静脉闭塞（RVO）模型视网膜水肿的治疗效果：方法：利用激光诱导小鼠视网膜静脉阻塞（RVO）模型，在静脉阻塞后多次给小鼠滴入马来酸噻吗洛尔和拉坦前列素眼药水。随后，研究人员检测了核内层（INL）的厚度以及作为内质网应激标记的 Vegf 和 Atf4 等基因的表达水平。在缺氧条件下用噻吗洛尔处理原代人类培养的视网膜微血管内皮细胞（HRMECs），然后研究其基因表达模式。重要的是，在 RVO 模型中使用了一种综合应激反应抑制剂（ISRIB），已知 ISRIB 能抑制视网膜水肿中 ATF4 的表达：结果：在RVO模型中，噻吗洛尔滴眼液抑制了INL厚度的增加，也抑制了Vegf和ATF4的表达。然而，拉坦前列腺素滴眼液并未引起INL厚度的任何变化。在HRMECs中，缺氧应激和血清缺失会增加Vegf和Atf4的表达；噻吗洛尔治疗会抑制Vegf的表达。此外，ISRIB还能减少与RVO相关的Vegf表达模式和水肿形成：这些结果表明，噻吗洛尔滴眼液可能是治疗 RVO 的一种潜在选择。

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

Molecular Vision 生物-生化与分子生物学

CiteScore

4.40

自引率

0.00%

发文量

审稿时长

1 months

期刊介绍： Molecular Vision is a peer-reviewed journal dedicated to the dissemination of research results in molecular biology, cell biology, and the genetics of the visual system (ocular and cortical). Molecular Vision publishes articles presenting original research that has not previously been published and comprehensive articles reviewing the current status of a particular field or topic. Submissions to Molecular Vision are subjected to rigorous peer review. Molecular Vision does NOT publish preprints. For authors, Molecular Vision provides a rapid means of communicating important results. Access to Molecular Vision is free and unrestricted, allowing the widest possible audience for your article. Digital publishing allows you to use color images freely (and without fees). Additionally, you may publish animations, sounds, or other supplementary information that clarifies or supports your article. Each of the authors of an article may also list an electronic mail address (which will be updated upon request) to give interested readers easy access to authors.