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R Iezzi, TL Walraven, JP McAllister, R Givens, G Auner, G Abrams; Biocompatibility of Caging Chromophores for Use in Retinal and Cortical Visual Prostheses . Invest. Ophthalmol. Vis. Sci. 2002;43(13):4478.
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Purpose: Visual prostheses based upon phototriggerable caged neurotransmitters include microfluidic and waveguide circuits to respectively activate and deliver stimulatory molecules to their sites of action. Photolytic cleavage of the caging chromophore results in the liberation of an active neurotransmitter and unbound cage. The design of a caged neurotransmitter must consider the wavelength and quantum efficiency of photolysis, in addition to the biocompatibility of the caging chromophore. Previous work by Givens et. al demonstrated that methoxy substitution of the p-hydroxyacetophenone (pHP) caging chromophore resulted in photolysis at longer wavelengths. The purpose of this study was to assess the biocompatibility of unsubstituted, mono and di-methoxy substituted pHP caging chromophores for their potential use in a neurotransmitter-based retinal or visual cortical prosthetic device. Methods: Visual cortical neurons were cultured from 19-day embryonic Sprague-Dawley rat pups and plated onto poly-d-lysine coated glass coverslips. After 8 days in culture, cells were exposed to pHP, p-hydroxy-m-methoxyacetophenone (MeO-pHP), p-hydroxy-m, m«-dimethoxyacetophenone (MeO)2-pHP [50 and 200uM]. Cellular viability and DNA degradation were assessed 6 hours after the initial exposure using trypan blue and TUNEL staining. Results: All chromophores demonstrated some level of cytotoxicity relative to control at [50 and 200 uM]. No increase of cytotoxicity was noted in the MeO-pHP relative to the pHP group at 50uM. Loss of trypan blue exclusion was inversely proportional to TUNEL positivity in all but the (MeO)2-pHP 200uM treatment group. Conclusion: The pHP chromophore offers neuroprotection to glutamate excitotoxicity when used as an L-glutamate cage. The moiety and its methoxy substitutions do demonstrate intrinsic neuronal cytotoxicity, however. Future work should consider modifications to pHP so as to minimize this intrinsic cytotoxicity. View OriginalDownload SlideView OriginalDownload Slide
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