Anti-Syndecan 2 Antibody Treatment Reduces Edema Formation and Inflammation of Murine Laser-Induced CNV.

IF 2.6 3区 医学 Q2 OPHTHALMOLOGY Translational Vision Science & Technology Pub Date : 2025-01-02 DOI:10.1167/tvst.14.1.10
Federico Corti, Filippo Locri, Flavia Plastino, Paola Perrotta, Krisztina Zsebo, Emma Ristori, Xiangyun Yin, Eric Song, Helder André, Michael Simons
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Abstract

Purpose: Alteration of visual acuity in wet age-related macular degeneration (AMD) is mostly driven by vascular endothelial growth factor A (VEGF-A)-induced edema from leaky newly forming blood vessels below the retina layers. To date, all therapies aimed at alleviation of this process have relied on inhibition of VEGF-A activity. Although effective in preventing vascular leak and edema, this approach also leads to the loss of normal vasculature and multiple related side effects.

Methods: We have developed an alternative strategy that uses anti-syndecan-2 polyclonal antibody (anti-Sdc2 pAb) to block VEGF-A-induced permeability without interfering with other VEGF-A activities. The effect of anti-Sdc2 pAb therapy was assessed in vitro using a transendothelial electrical resistance (TEER) assay, as well as staining of the endothelial cell junction, and in vivo in the laser-induced choroidal neovascularization (CNV) model.

Results: Anti-Sdc2 pAb blocked VEGF-A-induced permeability in vitro, and both local intravitreal injections and systemic intravenous treatments with anti-Sdc2 pAb were as effective as intravitreal anti-VEGF therapy in reducing edema, size of retinal lesions, and local inflammation in this model. Post-injury neovascularization was not affected by treatment with anti-Sdc2 pAb.

Conclusions: These findings indicate that anti-Sdc2 pAb therapy can be an effective alternative to anti-VEGF-A approaches for suppression of edema and to prevent retinal lesions in wet neovascular AMD (nAMD).

Translational relevance: Intravitreal anti-Sdc2 treatment may avoid side effects observed with the long-term anti-VEGF therapy, and systemic treatment with an anti-Sdc2 pAb antibody can address the issues associated with repeated intravitreal injections.

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抗syndecan 2抗体治疗可减少小鼠激光诱导CNV的水肿形成和炎症。
目的:湿性年龄相关性黄斑变性(AMD)的视力改变主要是由血管内皮生长因子A (VEGF-A)诱导的视网膜层下新血管渗漏引起的水肿引起的。迄今为止,所有旨在缓解这一过程的疗法都依赖于抑制VEGF-A活性。虽然可以有效防止血管渗漏和水肿,但这种方法也会导致正常血管的丧失和多种相关的副作用。方法:我们开发了一种替代策略,使用抗syndecan-2多克隆抗体(anti-Sdc2 pAb)来阻断VEGF-A诱导的渗透性,而不干扰其他VEGF-A活性。抗sdc2 pAb治疗的效果在体外通过跨内皮电阻(TEER)测定和内皮细胞连接染色来评估,在体内通过激光诱导脉络膜新生血管(CNV)模型来评估。结果:抗sdc2 pAb在体外阻断vegf - a诱导的通透性,在该模型中,局部玻璃体内注射和全身静脉注射抗sdc2 pAb在减少水肿、视网膜病变大小和局部炎症方面与玻璃体内抗vegf治疗同样有效。抗sdc2 pAb治疗不影响损伤后新生血管的形成。结论:这些研究结果表明,抗sdc2 pAb治疗可以有效替代抗vegf - a方法,抑制水肿和预防湿性新生血管性AMD (nAMD)的视网膜病变。翻译相关性:玻璃体内抗sdc2治疗可以避免长期抗vegf治疗所观察到的副作用,并且用抗sdc2 pAb抗体进行全身治疗可以解决反复玻璃体内注射相关的问题。
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
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.
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