Retinal inflammation: Novel drug delivery

Orlando-Nanomedicine that targets activated microglia and neuro-inflammation may one day be a potential therapy for age-related macular degeneration (AMD), diabetic retinopathy, and other eye diseases, said Rangaramanujam Kannan, PhD.

Dr. Kannan, professor of ophthalmology and co-director of the Center for Nanomedicine, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, focused on hydroxyl-terminated polyamidoamine (PAMAM) dendrimers.

He described dendrimers as tree-like polymers that can delivery targeted therapy. Dendrimers have an intrinsic ability to localize in activated microglia in the retina and brain. Microglia play a key role in the pathogenesis of photoreceptor and retinal pigment epithelial cell loss in AMD and retinitis pigmentosa, said Dr. Kannan at the 2014 meeting of the Association for Research in Vision and Ophthalmology.

However, microglia present both a problem and an opportunity in the realm of disease, he said.

“We think of inflammation, especially microglia, not only as a problem to shut down but also as an opportunity for therapeutic target,” Dr. Kannan said.

The goal of the therapy is to try to control the behavior of the activated microglias and macrophages.

The therapeutic use of PAMAM dendrimers has already been tested in animal models of cerebral palsy, where postnatal systemic therapy was used for prenatal injury, Dr. Kannan said. There is also research under way with dendrimers for autism, spinal cord injuries, and cancer, as well as retinal neuro-inflammation.

In research under way at the Wilmer Eye Institute, Dr. Kannan and colleagues are finding that dendrimers can remain in the body for an extended period (e.g., 30 days) and can potentially reduce or prevent choroidal neovascularization.

“Dendrimers have unique, intrinsic biodistribution,” Dr. Kannan said.

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