Featured Research

from universities, journals, and other organizations

Emerging pharmaceutical platform may pose risks to retinal health, study suggests

Date:
October 12, 2011
Source:
University of Kentucky
Summary:
An emerging pharmaceutical platform used in treating a variety of diseases may produce unintended and undesirable effects on eye function, according to a new study.

According to new research by University of Kentucky investigators, an emerging pharmaceutical platform used in treating a variety of diseases may produce unintended and undesirable effects on eye function. The paper, "Short-interfering RNAs Induce Retinal Degeneration via TLR3 and IRF3," appears in the current online edition of the journal Molecular Therapy, a publication of the Nature Publishing Group and the American Society of Gene and Cell Therapy.

"Short-interfering RNA (siRNA) technology has been regarded as one of the most exciting emerging platforms for new pharmaceuticals, said Dr. Jayakrishna Ambati, professor of physiology, and professor and vice chair of ophthalmology and visual sciences at UK.

To this point, siRNA drugs have been the subject of clinical trials past and present for a variety of disorders including: cancers, viral respiratory infections, hypercholesterolemia, macular degeneration, diabetic retinopathy and glaucoma. Major obstacles to realizing the therapeutic potential of siRNAs include delivery of the drug into cells and a generic suppression of blood vessel growth through immune activation, as shown by a 2008 paper from the Ambati group in the journal Nature.

"We now show a new undesirable effect of siRNAs that are 21 nucleotides or longer in length: these siRNAs, regardless of their sequence or target, can cause retinal toxicity. By activating a new immune pathway consisting of the molecules TLR3 and IRF3, these siRNAs damage a critical layer of the retina called the retinal pigmented epithelium (RPE). Damage to the RPE cells by siRNAs can also lead to secondary damage to the rods and cones, which are light-sensing cells in the retina," said Ambati.

The scientists' findings indicate that caution should be applied when designing or using siRNAs intended for either direct application to the eye, or intended for use in a way that may allow the drug to access the eye.

"Another novel aspect of this research is that the RPE degeneration caused by siRNAs resembles the pathology seen in the advanced form of age-related macular degeneration called geographic atrophy, said Ambati. "As there are few models of geographic atrophy, which affects millions of people worldwide, this paper provides an important advance for research in developing new treatments for this disease."

Because the research shows that siRNAs shorter 21 nucleotides in length can evade the TLR3-IRF3 off-target immune response, it may be possible to achieve therapeutic effects without retinal damage by designing shorter siRNAs.

This research was supported by the National Eye Institute, the Doris Duke Charitable Foundation, the Burroughs Wellcome Fund, and Research to Prevent Blindness, and was a collaboration with Yonsei University in Korea, Nagoya University, Mie University, Kyoto University in Japan and the University of Utah.


Story Source:

The above story is based on materials provided by University of Kentucky. Note: Materials may be edited for content and length.


Journal Reference:

  1. Mark E Kleinman, Hiroki Kaneko, Won Gil Cho, Sami Dridi, Benjamin J Fowler, Alexander D Blandford, Romulo JC Albuquerque, Yoshio Hirano, Hiroko Terasaki, Mineo Kondo, Takashi Fujita, Balamurali K Ambati, Valeria Tarallo, Bradley D Gelfand, Sasha Bogdanovich, Judit Z Baffi, Jayakrishna Ambati. Short-interfering RNAs Induce Retinal Degeneration via TLR3 and IRF3. Molecular Therapy, 2011; DOI: 10.1038/mt.2011.212

Cite This Page:

University of Kentucky. "Emerging pharmaceutical platform may pose risks to retinal health, study suggests." ScienceDaily. ScienceDaily, 12 October 2011. <www.sciencedaily.com/releases/2011/10/111011145723.htm>.
University of Kentucky. (2011, October 12). Emerging pharmaceutical platform may pose risks to retinal health, study suggests. ScienceDaily. Retrieved August 22, 2014 from www.sciencedaily.com/releases/2011/10/111011145723.htm
University of Kentucky. "Emerging pharmaceutical platform may pose risks to retinal health, study suggests." ScienceDaily. www.sciencedaily.com/releases/2011/10/111011145723.htm (accessed August 22, 2014).

Share This




More Health & Medicine News

Friday, August 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Drug Used To Treat 'Ebola's Cousin' Shows Promise

Drug Used To Treat 'Ebola's Cousin' Shows Promise

Newsy (Aug. 21, 2014) An experimental drug used to treat Marburg virus in rhesus monkeys could give new insight into a similar treatment for Ebola. Video provided by Newsy
Powered by NewsLook.com
Two US Ebola Patients Leave Hospital Free of the Disease

Two US Ebola Patients Leave Hospital Free of the Disease

AFP (Aug. 21, 2014) Two American missionaries who were sickened with Ebola while working in Liberia and were treated with an experimental drug are doing better and have left the hospital, doctors say on August 21, 2014. Duration: 01:05 Video provided by AFP
Powered by NewsLook.com
Cadavers, a Teen, and a Medical School Dream

Cadavers, a Teen, and a Medical School Dream

AP (Aug. 21, 2014) Contains graphic content. He's only 17. But Johntrell Bowles has wanted to be a doctor from a young age, despite the odds against him. He was recently the youngest participant in a cadaver program at the Indiana University NW medical school. (Aug. 21) Video provided by AP
Powered by NewsLook.com
American Ebola Patients Released: What Cured Them?

American Ebola Patients Released: What Cured Them?

Newsy (Aug. 21, 2014) It's unclear whether the American Ebola patients' recoveries can be attributed to an experimental drug or early detection and good medical care. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins