Hitching a ride into the retina on nanoparticles called dendrimers offers a new way to treat age-related macular degeneration and retinitis pigmentosa. A study by investigators at Mayo Clinic, Wayne State University and Johns Hopkins Medicine shows that steroids attached to the dendrimers target the damage-causing cells associated with neuroinflammation, leaving the rest of the eye unaffected and preserving vision.
The findings appear in the journal Biomaterials.
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. 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," says Mayo Clinic ophthalmologist Raymond Iezzi, M.D., a lead author of the study. "An effective treatment could offer hope to hundreds of millions of patients worldwide."
Iezzi and fellow principal author Rangaramanujam Kannan, Ph.D., an ophthalmology professor at The Wilmer Eye Institute of Johns Hopkins, developed an intracellular, sustained-release drug delivery system. The research, conducted in part at Wayne State University's Kresge Eye Institute with collaboration from Wayne State's College of Engineering and Ligon Research Center of Vision, tested the dendrimer delivery system in rats that develop neuroinflammation.
The target was microglial cells, inflammatory cells in charge of cleaning up dead and dying material in the eye, Dr. Iezzi says. When activated as "trash collectors," the cells cause damage via neuroinflammation -- a hallmark of each disease. The microglial cells gobble up the dendrimers, and the drug then shuts down the cells' activity.
"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," Kannan says.
The treatment reduced neuroinflammation in the rat model and protected vision by preventing injury to photoreceptors in the retina. Though the steroid offers only temporary protection, the treatment as a whole provides sustained relief from neuroinflammation.
The study was funded by grants from the Ligon Research Center of Vision at Wayne State University, the Ralph C. Wilson Foundation and Research to Prevent Blindness.
Co-authors include Bharath Raja Guru, Ph.D., Case Western Reserve University; Inna Glybina and Alexander Kennedy, both of Wayne State University; and Manoj Mishra, Ph.D., of Johns Hopkins University.
- Raymond Iezzi, Bharath R. Guru, Inna V. Glybina, Manoj K. Mishra, Alexander Kennedy, Rangaramanujam M. Kannan. Dendrimer-based targeted intravitreal therapy for sustained attenuation of neuroinflammation in retinal degeneration. Biomaterials, 2011; DOI: 10.1016/j.biomaterials.2011.10.010
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