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Our current research explores the applications of sound, light, and nanoparticles in ophthalmology. Specifically, we consider glaucoma, a common blinding disease associated with dysfunction of the trabecular meshwork (TM), a fluid drainage tissue in the anterior eye. A promising treatment involves delivery of stem cells to the TM to restore tissue function. To expedite clinical translation, non-invasive longitudinal monitoring of stem cell delivery in vivo is desired. We thus investigated ultrasound (US) and photoacoustic (PA) imaging of nanotracer-labeled mesenchymal stem cells (MSCs) and magnetic guidance of cells to the TM in the eye. Adipose-derived MSCs were incubated with photoacoustic nanoparticles to label cells (PA-MSCs), and 1000-4000 cells/µl were delivered to porcine eyes ex vivo while US/PA imaging was performed. Eyes were dissected for histology and additional spectroscopic PA imaging. Results show proof-of-concept for longitudinal detection of cell delivery using gold nanospheres and magnetically-mediated guidance using photomagnetic nanocubes. As cell number increased, the amplitude of spectroscopically unmixed signal from PA-MSCs increased, showing potential for quantitative imaging. Three-dimensional spectroscopic PA imaging and histology of the TM showed a similar ring-like morphology, with concentrations of signal from fluorescently-tagged cells matching the distribution of PA signal from the PA-MSCs. These results provide proof-of-concept for monitoring MSC ocular delivery, indicating new opportunities for development of nanoparticle-augmented imaging technologies in ophthalmic research. Tracking MSCs loaded with gold nanospheres has also provided new insights for improving delivery efficiency with photomagnetic nanoparticles, novel light delivery systems for safe, sensitive detection, and even a more physiologically relevant glaucoma model.
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