New mRNA vaccine shows promise for preventing blindness

Excessive blood vessel growth in the retina at the back of the eye is a primary driver of blindness in older individuals. The process, called neovascularization, is at the root of such diseases as age-related macular degeneration, or AMD. Vision blurs, distorts, and in most cases is permanently lost as the leaking vessels spill fluid into the retina. Current treatment entails frequent injections directly into the eye, a painful and time-consuming process that many patients have difficulty maintaining.

Now, scientists in Japan have created a potentially more effective and comfortable option: an mRNA vaccine delivered by a simple shot in the arm. The vaccine cut the formation of harmful blood vessels in the retina by more than half in mouse experiments, bringing hope to millions of people worldwide at risk of vision loss from AMD and other diseases.

For nearly two decades, anti-VEGF drugs have been the go-to therapy for wet AMD, the form of the disease linked to leaking blood vessels. The drugs are effective at slowing the disease but must be injected into the eye as often as once a month. Some patients stop responding over time, while others give up because of the discomfort and repeated trips to the clinic. In spite of best compliance, vision continues to be lost by most people over the years.

That challenge led researchers at the Institute of Science Tokyo and Yokohama City University to look for a less invasive, more long-term solution. Their suggestion was to utilize the same mRNA technology that powered the COVID-19 vaccines, but redirect it to fight a protein that promotes blood vessel growth in the retina.

Led by Professor Satoshi Uchida and Visiting Professor Yasuo Yanagi, the scientists developed a vaccine that carries mRNA instructions for leucine-rich alpha-2-glycoprotein 1, or LRG1. The protein is closely linked to abnormal blood vessel growth but is not essential for normal blood flow. Injected, the mRNA directs cells to make a harmless form of LRG1, which prompts the immune system to create antibodies that block it.

The COVID-19 pandemic showed us the remarkable potential of mRNA as a vaccine platform," Uchida said. "Encouraged by those successes, we wondered whether we could apply it to chronic eye disease, along with infectious disease and cancer. To our knowledge, this is the first paper to show that an mRNA vaccine can potentially suppress pathological neovascularization in animal models.".

The vaccine uses lipid nanoparticles—tiny bubbles similar to fat—to safely deliver the fragile mRNA into muscle cells. Mice received two doses, two weeks apart, on a typical vaccination schedule. After the booster shot, antibody levels against LRG1 skyrocketed, a sign that the animals' immune systems were primed to fight the disease.

The researchers tested their vaccine in two established mouse models of neovascularization. In one, they used lasers to cause new vessel growth, which is similar to what happens in human macular degeneration. The other model used genetically engineered mice that develop the condition on their own.

The results were striking. In the laser model, mice that had been vaccinated had 85% less leakage of blood vessels and 82% less lesion size compared to unvaccinated mice. In the genetic model, the vaccine decreased the area of abnormal vessels by 40% at three weeks and 55% at four weeks.

Importantly, treatment also reduced the amount of inflammatory cells in the retina, a sign that it calmed damaging immune response as well as blocking vessel growth. Also noteworthy, the vaccine did not damage healthy tissue or interfere with normal blood vessel function.

One of the biggest concerns regarding vaccines for natural proteins is inducing autoimmune responses, where the immune system mistakenly attacks healthy tissue. To think about this, the scientists searched for signs of inflammation or organ damage. They didn't observe any side effects in the eyes, liver, or other organs of vaccinated mice. Immune cells were confined to the injection site, and liver enzyme levels were typical.

However, the researchers caution that much more work needs to be done before the vaccine could be tested in humans. No one knows how long the protection would endure, what dose would be effective, or if the same results will hold true in humans. The study findings, published in the journal Vaccine, are an early but important move toward a new approach to treating eye disease.

If this study succeeds in translating to humans, it has the potential to transform eye care for millions of individuals suffering from AMD and similar diseases. Rather than undergoing repeated eye injections, patients might get a short arm injection once or twice, with effects that would last considerably longer.

This treatment would be more convenient for patients, save healthcare systems money, and preserve vision in aging populations globally.

Aside from AMD, the study also illustrates how mRNA vaccines could be designed to treat other chronic conditions driven by harmful proteins, extending the reach of this flexible technology far beyond infectious disease.

Research findings are available online in the journal ScienceDirect.

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