The retinal pigment epithelium (RPE) and choroidal vasculature play important roles in the pathophysiology of age-related macular degeneration (AMD), a leading cause of blindness in the elderly. Current therapeutic strategies rely on intravitreal or subretinal injections to deliver the pharmacologic agents. However, these injections are invasive and costly, and may adversely affect other ocular structures. The goal of this study is to develop a drug delivery system that could be given intravenously, and directly targeted to RPE or choroidal vessels for the treatment of retinal diseases like AMD. Our hypothesis is that nanoporphyrins, a multifunctional porphyrin/cholic acid-based micellar nanoparticle, that can 1) efficiently encapsulate fluorescent dyes or pharmacologic compounds, 2) release the payload when triggered with an external light source, and 3) be decorated with tissue-specific ligands, can be used to provide both diagnostic and therapeutic functions in the eye. Using confocal scanning laser ophthalmoscopy (SLO) technology, nanoporphyrins can be visualized and triggered to release a drug directly to RPE or CECs.
The specific aims of this study are to 1) to discover RPE and CEC-specific peptide ligands using combinatorial library screening, 2) to visualize and trigger nanoporphyrins in mouse eyes using SLO imaging, and 3) to test transducers that efficiently convert light to heat for photothermal therapy (PTT) and to singlet oxygen for PDT, similAs an academic clinician-scientist and vitreoretinal specialist, I have both clinical and research interests in As an academic clinician-scientist and vitreoretinal specialist, I have both clinical and research interests in understanding the mechanisms of retinal diseases. With a strong background in neuronal cell culture and clinical ophthalmic imaging, I am well-prepared to pursue translational research to study the pathogenesis and treatment of AMD. UC Davis offers a world-class faculty and facilities that has the potential to facilitate my training in areas of nanotherapeutics, drug delivery, and live animal ocular imaging. The mentoring and skills acquired with this grant proposal will enable me to attain expertise in translational AMD research.

Public Health Relevance

Age-related macular degeneration (AMD) is a leading cause of blindness in the elderly, but current therapies rely on intraocular injections which are costly and invasive. This research seeks to develop and test a nanoparticle delivery system that can be given intravenously, targeted to specific cell types in the eye, and triggered to release the drug using a non-invasive external light source. This highly-specific and observable drug delivery platform will have important translational potential for the treatment of AMD and other retinal diseases.

National Institute of Health (NIH)
National Eye Institute (NEI)
Clinical Investigator Award (CIA) (K08)
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Special Emphasis Panel (ZEY1)
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Agarwal, Neeraj
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University of California Davis
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