Nav: Home

New RNAi treatment targets eye inflammation

February 13, 2017

Scientists have developed a new RNA interference (RNAi) therapeutic agent that safely blocked ocular inflammation in mice, potentially making it a new treatment for human uveitis and diabetic retinopathy.

Inflammation plays a central role in vision-threatening eye diseases such as age-related macular degeneration and diabetic retinopathy. More commonly, it causes uveitis, or inflammation of the uvea, the pigmented middle layer of the eye. Uveitis causes redness, pain and blurred vision, requiring urgent treatment to prevent complications, including blindness.

A common treatment for uveitis is applying anti-inflammatory steroid eye drops. Steroid pills or even injections may be necessary in severe cases. However, long-term steroid use may cause systemic and ocular side-effects, including hypertension and glaucoma, respectively.

Now, researchers led by Susumu Ishida and Atsuhiro Kanda at Hokkaido University's Graduate School of Medicine have shown that the activation of the receptor-associated prorenin system (RAPS) is involved in the pathogenesis of uveitis. The research was conducted in collaboration with BONAC Corporation and reported recently in Molecular Therapy: Nucleic Acids.

The RAPS has been shown to be involved in the pathogenesis of various vascular abnormalities such as inflammation and pathological angiogenesis. Therefore, drugs targeting the RAPS may result in beneficial effects on various vascular disorders, including uveitis and diabetic retinopathy.

Ishida's team showed that a molecule called the (pro)renin receptor, which activates the RAPS, significantly increased in the vitreous fluid of 22 patients with uveitis compared to normal controls. In addition, there was a positive relationship between increased intraocular levels of a soluble form of the (pro)renin receptor and monocyte chemotactic protein-1, a known inflammatory mediator in uveitis as well as in diabetic retinopathy.

The researchers then developed a new type of single-strand RNA interference (RNAi) agent, the proline-modified short hairpin RNA (PshRNA), which suppresses gene expression by utilizing the cellular system. The team designed the PshRNA agent selectively targeting the common sequence of human and mouse (pro)renin receptor genes.

After testing the suppressive efficacy of the PshRNA agent in cultured cells, they injected it into the mouse's eyes. The results demonstrated that this new molecule was safe and effective, causing significant improvement in mouse models of both acute uveitis and chronic diabetic inflammation, with no apparent side-effects.

"Our findings suggest significant involvement of the (pro)renin receptor in human uveitis, as well as the potential use of the PshRNA agent to reduce ocular inflammation," says Atsuhiro Kanda.
-end-


Hokkaido University

Related Inflammation Articles:

TWEAKing inflammation
Superficially, psoriasis and atopic dermatitis may appear similar but their commonalities are only skin deep.
More than a 'gut feeling' on cause of age-associated inflammation
Bowdish and her colleagues raised mice in germ-free conditions and compared them to their conventionally raised counterparts.
Inflammation: It takes two to tango
Signal molecules called chemokines often work in tandem to recruit specific sets of immune cells to sites of tissue damage.
Inflammation awakens sleepers
The inflammatory response that is supposed to ward off pathogens that cause intestinal disease makes this even worse.
Inflammation in regeneration: A friend or foe?
Scientists at Tokyo Institute of Technology have discovered a novel mechanism linking inflammation and organ regeneration in fish, which can be conserved among vertebrates.
New RNAi treatment targets eye inflammation
Scientists have developed a new RNA interference (RNAi) therapeutic agent that safely blocked ocular inflammation in mice, potentially making it a new treatment for human uveitis and diabetic retinopathy.
Every meal triggers inflammation
When we eat, we do not just take in nutrients -- we also consume a significant quantity of bacteria.
Inflammation halts fat-burning
Scientists at the University of Bonn have shown in mice that excess pounds can simply be melted away by converting unwanted white fat cells into energy-consuming brown slimming cells.
New tool uses UV light to control inflammation
Cornell researchers have developed a chemical tool to control inflammation that is activated by ultraviolet (UV) light.
Myocardial inflammation elevated in RA patients
Two new studies measure the prevalence of myocardial inflammation in RA patients without known cardiovascular disease, assess how it is associated with high disease activity and show how disease-modifying therapy may decrease this type of inflammation, according to new research findings presented this week at the 2016 ACR/ARHP Annual Meeting in Washington.

Related Inflammation Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Bias And Perception
How does bias distort our thinking, our listening, our beliefs... and even our search results? How can we fight it? This hour, TED speakers explore ideas about the unconscious biases that shape us. Guests include writer and broadcaster Yassmin Abdel-Magied, climatologist J. Marshall Shepherd, journalist Andreas Ekström, and experimental psychologist Tony Salvador.
Now Playing: Science for the People

#514 Arctic Energy (Rebroadcast)
This week we're looking at how alternative energy works in the arctic. We speak to Louie Azzolini and Linda Todd from the Arctic Energy Alliance, a non-profit helping communities reduce their energy usage and transition to more affordable and sustainable forms of energy. And the lessons they're learning along the way can help those of us further south.