July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Delivery and Toxicity of Ruthenium Pyridine-based Nanophotoswitches in Retina
Author Affiliations & Notes
  • Melanie Pribisko
    Chemistry, California Institute of Technology, Pasadena, California, United States
    Chemistry, California State University Channel Islands, Camarillo, California, United States
  • Uli Herget
    Chemistry, California Institute of Technology, Pasadena, California, United States
  • Lan Yue
    USC Keck School of Medicine, Los Angeles, California, United States
  • Ming-yi Lin
    USC Keck School of Medicine, Los Angeles, California, United States
  • Robert H Chow
    USC Keck School of Medicine, Los Angeles, California, United States
  • Mark S. Humayun
    USC Keck School of Medicine, Los Angeles, California, United States
  • Robert H Grubbs
    Chemistry, California Institute of Technology, Pasadena, California, United States
  • Harry Gray
    Chemistry, California Institute of Technology, Pasadena, California, United States
  • Footnotes
    Commercial Relationships   Melanie Pribisko, None; Uli Herget, None; Lan Yue, None; Ming-yi Lin, None; Robert Chow, None; Mark Humayun, None; Robert Grubbs, None; Harry Gray, None
  • Footnotes
    Support  NSF AIRTT
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 232. doi:
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      Melanie Pribisko, Uli Herget, Lan Yue, Ming-yi Lin, Robert H Chow, Mark S. Humayun, Robert H Grubbs, Harry Gray; Delivery and Toxicity of Ruthenium Pyridine-based Nanophotoswitches in Retina. Invest. Ophthalmol. Vis. Sci. 2018;59(9):232.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Nanophotoswitches (NPSs) offer a new tool for optical stimulation of neuronal activity, in vitro and potentially in vivo. Our group previously reported a ruthenium bipyridine (Rubpy)-based NPS (Rubpy-C17) that, after injection into the eyes of photoreceptor degenerated blind rats, elicited electrical activity in the contralateral superior colliculus upon light illumination. We wish to optimize delivery, efficacy and biosafety of the NPSs; our preliminary experiments examining the Rubpy complexes in vivo suggest low acute toxicity. Intravitreal delivery of the Rubpy-C17 complexes has been shown to restore light response recorded from the superior colliculus of the photoreceptor degenerate RCS rats 1 day after the injection. The restored light response was largely preserved 3 days after the injection, suggesting that the Rubpy-C17 complexes are well tolerated by the retinal neurons during the test period.

Methods : Promising NPSs molecules absorb and can be visualized by their luminescence upon visible wavelength illumination. This enables us to evaluate the toxicity of the NPSs using an array of in vitro, in vivo and ex vivo tests, including in vitro electrochemical and spectroscopic studies to determine DNA binding and DNA intercalation. In addition, the NPSs were embedded in polymer matrices and the emission monitored to determine the rate of release upon injection into the eye.

Results : Preliminary data show that young zebrafish tolerate injection of up to 100 uM Rubpy-C17 into the eye, with complete disappearance of the Rubpy-C17 emission from the eye within a day. Interestingly, blue-green emission appears in the liver region as the orange-red emission of Rubpy-C17 decreases. As this may be a result of metabolism of the Rubpy-C17, we extracted the blue-green emitting molecule for characterization. Initial studies of slow-release drug delivery system and conditions indicate some success with polyethyleneglycol-poly(lactic-co-glycolic acid)-poly-L-lysine (PEG-PLGA-PEG) and polycaprolactone (PCL) polymers.

Conclusions : Our data suggest that NPSs dissolved in a DMSO solution and intravitreally administered remain stable and active in the ocular environment up to at least one day post injection, which can be extended when coadministered with certain polymer mixtures. The DNA binding and DNA intercalation studies, in combination with the extended release polymers, address toxicity concerns of the NPSs in the eye.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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