Summary: Japanese researchers have developed an mRNA vaccine that suppresses abnormal blood vessel growth in the retina of mice, offering a promising, less invasive alternative for treating age-related macular degeneration (AMD). Unlike current therapies that require repeated injections directly into the eye, this vaccine is administered intramuscularly.
By targeting leucine-rich alpha-2-glycoprotein 1 (LRG1)—a protein linked to pathological angiogenesis—the vaccine induced strong antibody responses and reduced retinal damage by as much as 85% in mouse models. If translated to humans, this approach could significantly reduce the need for frequent ocular injections and ease the treatment burden for patients with wet AMD and other neovascular eye diseases.
Key Facts
- Mechanism: Elicits antibodies that block LRG1, a driver of abnormal blood vessel growth.
- Effectiveness: In mouse models, retinal leakage decreased by 85% and lesion size by up to 82%.
- Advantage: Comparable efficacy to anti-VEGF therapy but delivered as a simple intramuscular injection.
Source: Institute of Science Tokyo
An mRNA vaccine developed by researchers in Japan significantly reduced pathological neovascularization in mouse retinas.
Neovascularization in the retina—an abnormal growth of blood vessels—is a hallmark of wet age-related macular degeneration (AMD), a leading cause of vision loss among people over 60. These fragile vessels leak fluid into the retina, progressively impairing vision. Current standard care relies on frequent intraocular injections of anti-angiogenic drugs, a regimen that can be burdensome and, in some cases, loses effectiveness over time.
Researchers at the Institute of Science Tokyo (Science Tokyo) created an mRNA vaccine designed for intramuscular injection that prompts the immune system to produce antibodies against LRG1. In multiple mouse models of retinal disease, this vaccine markedly suppressed retinochoroidal neovascularization, suggesting a potential new therapeutic strategy for AMD and related conditions.
AMD affects nearly 200 million people worldwide and is a major cause of vision impairment in older adults. Wet AMD arises when abnormal choroidal vessels invade the retina and leak fluid, forming lesions that damage central vision. Current anti-VEGF injections into the eye are effective but require frequent dosing and can be difficult for patients to maintain.
Led by Professor Satoshi Uchida (Department of Advanced Nanomedical Engineering, Science Tokyo) and Visiting Professor Yasuo Yanagi (Department of Ophthalmology and Micro-technology, Yokohama City University), the research team evaluated the LRG1-targeting mRNA vaccine in two established mouse models: a laser-induced choroidal neovascularization (CNV) model and a genetically predisposed model that develops CNV naturally.
Following two intramuscular injections given 14 days apart, both models mounted robust anti-LRG1 antibody responses. Effects were evident within one week of the first dose. By day 21 in the laser-induced model, vascular leakage fell by 85% and lesion size by 82%; in the natural NV model, lesion size decreased by 55% by day 28.
Importantly, the vaccine did not impair normal vascular development, harm healthy retinal tissue, or provoke damaging immune responses in other organs. Histological analysis showed preserved retinal architecture and no abnormal glial activation. The treatment’s impact on endothelial and microglial cell numbers was comparable to that of anti-VEGF antibody therapy, but achieved via systemic intramuscular delivery rather than repeated intravitreal injections.
“The success of mRNA technology in infectious disease vaccines inspired us to explore broader applications,” says Uchida. “This study provides the first evidence that an mRNA vaccine can mitigate pathological neovascularization in animal models, and it highlights LRG1 as a promising therapeutic target.”
If clinical trials confirm safety and efficacy in humans, an LRG1-targeting mRNA vaccine could shift AMD treatment from frequent eye injections to periodic intramuscular vaccinations, reducing discomfort and logistical challenges for patients and clinicians alike.
About this AMD and genetics research news
Author: Miki Yamaoka
Source: Institute of Science Tokyo
Contact: Miki Yamaoka – Institute of Science Tokyo
Image: The image is credited to Neuroscience News
Original Research: Open access.
“mRNA vaccination mitigates pathological retinochoroidal neovascularization in animal models” by Satoshi Uchida et al. Vaccine
Abstract
mRNA vaccination mitigates pathological retinochoroidal neovascularization in animal models
Retinochoroidal neovascularization (NV) contributes to vision loss in macular degeneration, diabetic retinopathy, and other ocular diseases. Current therapies depend on repeated intraocular injections of anti-angiogenic agents, which impose a heavy burden on patients and healthcare systems; some patients also experience limited or waning responses.
This study evaluates an mRNA vaccine designed to induce anti-LRG1 antibodies and thereby reduce pathological NV. In laser-induced NV models, LRG1 mRNA vaccination decreased NV area and vascular leakage and reduced microglial infiltration. Histology revealed no detrimental effects on retinal layers or glial activation. In Vldlr knockout mice, the vaccine suppressed ongoing neovascularization and downregulated key angiogenic mediators. These results support LRG1-targeted mRNA vaccination as a novel therapeutic strategy for CNV-associated eye diseases.