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Researchers At Hokkaido University Develop New RNAi Treatment Strategy

12.04.2017

Japanese researchers believe they've come up with an RNA interference (RNAi) therapy that could change how doctors deal with eye inflammation that results from vascular eye diseases. Although this therapy hasn't been tested on humans yet, there's great hope that this RNAi treatment will change how eye doctors deal with uveitis and diabetic retinopathy.

Eye diseases such as diabetic retinopathy and age-related macular degeneration often cause eye inflammation. In particular, these eye diseases cause uveitis, which is an inflammation of the pigmented area of the eye known as the uvea. Uveitis can cause pain and redness in the eyes and, if left untreated, could result in blindness.

A team of Japanese researchers at Hokkaido University's Graduate School of Medicine has shown that the receptor-associated prorenin system (RAPS) is always involved in the development of uveitis. This study's head researchers, Susumu Ishida and Atsuhiro Kanda, believe developing drugs that target RAPS may be the best way to deal with vascular eye conditions such as uveitis.

One molecule in particular piqued the interest of these doctors. Called the (pro)renin receptor, this molecule was found to be higher in patients with uveitis rather than patients without any vascular eye problem. Doctors measured the amount of (pro)renin receptors by taking a look at patients' vitreous fluid.

As they looked deeper into these vitreous fluid samples, researchers discovered (pro)renin receptors have a positive relationship with monocyte chemotactic protein-1. Monocyte chemotactic protein-1 is well known as an inflammatory mediator in both diabetic retinopathy and uveitis.

After looking into all this data, researchers developed their own single-strand RNAi agent to test on mice. This RNAi agent is officially called a proline-modified short hairpin RNA (PshRNA), and it has been shown to diminish gene expression through use of the cellular system. Researchers designed this PshRNA agent using data on both (pro)renin receptor genes taken from humans and mice.

The Japanese team first tested PshRNA in a group of cultured cells. After those tests proved successful, researchers injected PshRNA into the eyes of mice. All of the mice injected with this RNAi solution showed a great reduction in their uveitis or diabetic inflammation. No side effects were observed, and every mouse appeared healthy after the injection of PshRNA.

Kanda told reporters he believes this study will help scientists develop more effective treatment options for patients with vascular eye diseases. As Dr. Kanda put it, "Our findings suggest…the potential use of the Psh-RNA agent to reduce ocular inflammation."

Today, most eye doctors use anti-inflammatory steroid eye drops to control uveitis. More serious cases of uveitis may require steroid pills or injections. Unfortunately, this treatment strategy is not optimal since it often leads to the development of glaucoma and/or hypertension. The new data released by Hokkaido University will hopefully get patients off of potentially dangerous steroid pills and replace them with more stable RNAi therapies.

There's no word yet on whether or not researchers at Hokkaido University have any future tests planned for the Psh-RNA agent. Interested readers can check out the full study in the medical journal Molecular Therapy—Nucleic Acids. The study was published under the title "A novel single-strand RNAi therapeutic agent targeting (pro)renin receptor suppresses ocular inflammation."






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