Hitching a ride into the retina on nanoparticles called dendrimers offers a new way to treat age-related macular degeneration and retinitis pigmentosa. A collaborative research study among investigators at Wayne State University, the Mayo Clinic and Johns Hopkins Medicine shows that steroids attached to the dendrimers targeted the damage-causing cells associated with neuroinflammation, leaving the rest of the eye unaffected and preserving vision.
The principal authors of the study, Raymond Iezzi, M.D. (Mayo Clinic ophthalmologist) and Rangaramanujam Kannan, Ph.D. (faculty of ophthalmology at The Wilmer Eye Institute of Johns Hopkins) have developed a clinically relevant, targeted, sustained-release drug delivery system using a simple nanodevice construct. The experimental work in rat models was initiated and substantially conducted at Wayne State University, and showed that one intravitreal administration of the nanodevice in microgram quantities could offer neuroprotection at least for a month, and appears in the journal, Biomaterials (33(3), 979-988).
Both dry age-related macular degeneration and retinitis pigmentosa are caused by neuroinflammation, which progressively damages the retina and can lead to blindness. Macular degeneration is the primary cause of vision loss in older Americans, affecting more than 7 million people, according to the National Institutes of Health (NIH). Retinitis pigmentosa encompasses many genetic conditions affecting the retina and impacts 1 in 4,000 Americans, the NIH estimates.
"There is no cure for these diseases, said Iezzi. "An effective treatment could offer hope to hundreds of millions of patients worldwide. We tested the dendrimer delivery system in rats that develop neuroinflammation leading to retinal degeneration. The target was activated microglial cells, the immune cells in charge of cleaning up dead and dying material in the eye. When activated, these cells cause damage via neuroinflammation — a hallmark of each disease."
"Dendrimers are tree-like, non-cytotoxic polymeric drug delivery vehicles (~ 4 nm). Surprisingly, the activated microglia in the degenerating retina appeared to eat the dendrimer selectively and retain them for at least a month. The drug is released from the dendrimer in a sustained fashion inside these cells, offering targeted neuroprotection to the retina," said Kannan.
The treatment reduced neuroinflammation in the rat model and protected vision by preventing injury to photoreceptors in the retina. Although the steroid offers only temporary protection, the treatment as a whole provides sustained relief from neuroinflammation, the study found. The researchers believe that this patent-pending technology with significant translational potential will be advanced further, through this multi-university collaboration among Johns Hopkins, Mayo Clinic and Wayne State. The study was funded by grants from the Ligon Research Center of Vision at Wayne State University, the Ralph C. Wilson Medical Research Foundation, Office of the Vice President for Research at Wayne State University, and Research to Prevent Blindness.
The researchers declare no conflict of interest.
Co-authors include Bharath Raja Guru, Ph.D., Case Western Reserve University; Inna Glybina and Alexander Kennedy, Wayne State University; and Manoj Mishra, Ph.D., The Wilmer Eye Institute of Johns Hopkins.
Wayne State University is one of the nation's pre-eminent public research institutions in an urban setting. Through its multidisciplinary approach to research and education, and its ongoing collaboration with government, industry and other institutions, the university seeks to enhance economic growth and improve the quality of life in the city of Detroit, state of Michigan and throughout the world. For more information about research at Wayne State University, visit http://www.research.wayne.edu.
Julie O'Connor | EurekAlert!
Predicting a protein's behavior from its appearance
10.12.2019 | Ecole Polytechnique Fédérale de Lausanne
Could dark carbon be hiding the true scale of ocean 'dead zones'?
10.12.2019 | University of Plymouth
Graphene, a two-dimensional structure made of carbon, is a material with excellent mechanical, electronic and optical properties. However, it did not seem suitable for magnetic applications. Together with international partners, Empa researchers have now succeeded in synthesizing a unique nanographene predicted in the 1970s, which conclusively demonstrates that carbon in very specific forms has magnetic properties that could permit future spintronic applications. The results have just been published in the renowned journal Nature Nanotechnology.
Depending on the shape and orientation of their edges, graphene nanostructures (also known as nanographenes) can have very different properties – for example,...
Using a clever technique that causes unruly crystals of iron selenide to snap into alignment, Rice University physicists have drawn a detailed map that reveals...
University of Texas and MIT researchers create virtual UAVs that can predict vehicle health, enable autonomous decision-making
In the not too distant future, we can expect to see our skies filled with unmanned aerial vehicles (UAVs) delivering packages, maybe even people, from location...
With ultracold chemistry, researchers get a first look at exactly what happens during a chemical reaction
The coldest chemical reaction in the known universe took place in what appears to be a chaotic mess of lasers. The appearance deceives: Deep within that...
Abnormal scarring is a serious threat resulting in non-healing chronic wounds or fibrosis. Scars form when fibroblasts, a type of cell of connective tissue, reach wounded skin and deposit plugs of extracellular matrix. Until today, the question about the exact anatomical origin of these fibroblasts has not been answered. In order to find potential ways of influencing the scarring process, the team of Dr. Yuval Rinkevich, Group Leader for Regenerative Biology at the Institute of Lung Biology and Disease at Helmholtz Zentrum München, aimed to finally find an answer. As it was already known that all scars derive from a fibroblast lineage expressing the Engrailed-1 gene - a lineage not only present in skin, but also in fascia - the researchers intentionally tried to understand whether or not fascia might be the origin of fibroblasts.
Fibroblasts kit - ready to heal wounds
03.12.2019 | Event News
15.11.2019 | Event News
15.11.2019 | Event News
10.12.2019 | Architecture and Construction
10.12.2019 | Information Technology
10.12.2019 | Life Sciences