Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Emerging pharmaceutical platform may pose risks to retinal health

Short interfering RNAs induce retinal degeneration via TLR3 and IRF3

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 than 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.

The lead authors on this paper are Mark E. Kleinman, Assistant Professor of Ophthalmology & Visual Sciences, and Hiroki Kaneko and Won Gil Cho, also of UK. Other members of the UK research team in the Department of Ophthalmology & Visual Sciences include: Sami Dridi, Benjamin J. Fowler, Alexander D. Blandford, Yoshio Hirano, Valeria Tarallo, Bradley D. Gelfand, Sasha Bogdanovich and Judit Z. Baffi, Assistant Professor of Ophthalmology. Ambati is also the Dr. E. Vernon & Eloise C. Smith Endowed Chair in Macular Degeneration Research.

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.

Allison Elliott | EurekAlert!
Further information:

More articles from Health and Medicine:

nachricht Resolving the mystery of preeclampsia
21.10.2016 | Universitätsklinikum Magdeburg

nachricht New potential cancer treatment using microwaves to target deep tumors
12.10.2016 | University of Texas at Arlington

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

Im Focus: New Products - Highlights of COMPAMED 2016

COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.

In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...

Im Focus: Ultra-thin ferroelectric material for next-generation electronics

'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.

Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Resolving the mystery of preeclampsia

21.10.2016 | Health and Medicine

Stanford researchers create new special-purpose computer that may someday save us billions

21.10.2016 | Information Technology

From ancient fossils to future cars

21.10.2016 | Materials Sciences

More VideoLinks >>>