Scientists at Hokkaido University’s Graduate School of Medicine have successfully used RNA interference (RNAi) to block ocular inflammation in mice. It is hoped that the technique could be used to treat a range of inflammatory eye conditions such as diabetic retinopathy, uveitis and age-related macular degeneration, the latter being the main cause of blindness and low vision in the United States.
Uveitis is inflammation of the uvea or uveal tract – the pigmented layer in the eye. Uveitis can cause eye pain, soreness, blurred or cloudy vision, and loss of peripheral vision. If untreated, the condition can lead to blindness and a host of other medical complications. Uveitis often develops as a result of age-related macular degeneration and diabetic retinopathy.
Professor Susumu Ishida and his team of researchers have discovered that the receptor-associated prorenin system (RAPS) is involved in the pathogenesis of human uveitis, diabetic retinopathy, and other vascular abnormalities, therefore medications that target RAPS could potentially be of use in the treatment of these medical conditions.
The team determined that the (pro) renin receptor that activates RAPS was at a higher level in the vitreous humor of 22 patient suffering from uveitis, compared to the control group. Further, the team discovered a positive relationship between increased intraocular levels of a soluble form of the (pro) renin receptor and monocyte chemotactic protein-1, which is a known inflammatory mediator in uveitis and diabetic retinopathy.
The team then developed a novel RNAi agent – proline-modified short hairpin RNA (PshRNA) – to selectively suppress gene expression of (pro) renin receptor genes. After demonstrating gene suppression using the RNAi agent in vitro, the team injected PshRNA into mouse eyes. The team not only determined that injection of their new RNAi agent was safe, it also significantly reduced inflammation associated with acute uveitis and inflammation caused by diabetes. The team reports that there were no side effects associated with the treatment.
According to first author Assistant Professor Atsuhiro Kanda, “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.”