mRNA vaccination mitigates pathological retinochoroidal neovascularization in animal models

IF 4.5 3区医学 Q2 IMMUNOLOGY

Vaccine Pub Date : 2025-07-02 DOI:10.1016/j.vaccine.2025.127451

Yasuo Yanagi , Hinako Ichikawa , Le Bui Thao Nguyen , Akimasa Hayashi , Naoko Abe , Hiroshi Abe , Satoshi Uchida

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引用次数: 0

Abstract

Retinochoroidal neovascularization (NV), involved in macular degeneration, diabetic retinopathy, and other ocular diseases, causes vision impairment and blindness. Current treatments rely on repeated intraocular injections of anti-angiogenic drugs, which are burdensome for patients and clinicians, and some patients fail to respond to the treatments. This study investigates the potential of mRNA vaccination to mitigate NV and treat ocular pathologies. The vaccine targets leucine-rich alpha-2-glycoprotein 1 (LRG1), a protein specifically expressed in pathological neovascularization, inducing anti-LRG1 antibody responses in mice. In a laser-induced NV model, the LRG1 mRNA vaccine reduces NV area and leakage while inhibiting microglial cell infiltration. Histological analysis shows no adverse effects on retinal architecture or glial cell activation. Additionally, in Vldlr knockout mice, LRG1 mRNA administration suppresses ongoing neovascularization and downregulates key angiogenic mediators. These findings highlight the therapeutic potential of LRG1 mRNA as a novel strategy for CNV-associated diseases.

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mRNA疫苗可减轻动物模型中病理性视网膜脉络膜新生血管的形成

视网膜脉络膜新生血管（NV）与黄斑变性、糖尿病视网膜病变和其他眼部疾病有关，可导致视力损害和失明。目前的治疗依赖于反复眼内注射抗血管生成药物，这对患者和临床医生来说都是负担，而且一些患者对治疗没有反应。本研究探讨mRNA疫苗接种减轻NV和治疗眼部病变的潜力。该疫苗靶向富含亮氨酸的α -2糖蛋白1 (LRG1)，一种在病理性新生血管中特异性表达的蛋白，在小鼠中诱导抗LRG1抗体反应。在激光诱导NV模型中，LRG1 mRNA疫苗减少NV面积和渗漏，同时抑制小胶质细胞浸润。组织学分析显示对视网膜结构或神经胶质细胞活化无不良影响。此外，在Vldlr基因敲除小鼠中，LRG1 mRNA管理抑制正在进行的新生血管和下调关键的血管生成介质。这些发现突出了LRG1 mRNA作为cnv相关疾病的新策略的治疗潜力。

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

Vaccine 医学-免疫学

CiteScore

8.70

自引率

5.50%

发文量

992

审稿时长

131 days

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