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J. Winter, M. N. Gokhale, S. F. Cogan, J. F. Rizzo; Drug Delivery Systems to Promote Electrode-Host Integration in Retinal Prostheses. Invest. Ophthalmol. Vis. Sci. 2007;48(13):2566.
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To improve neuron-electrode integration in retinal prostheses through the incorporation of drug delivery and tissue engineered surfaces. The ultimate goal is to lower perceptual thresholds by reducing the separation distance between excitable elements (neurites) and electrodes.
This study examined neurite extension from PC12 cells and retinal explants in response to neurotrophin (either NGF or BDNF) delivery from polymeric poly(ethylene glycol)-poly(lactic acid) hydrogels applied to the retinal prosthesis surface. Additionally, because of the expected limited duration of drug release, the effect of cell adhesion molecules (e.g., laminin, collagen, and poly-L-lysine) on promoting chronic neurite extension/attachment following acute neurotrophin administration was examined. Neurite length and density was measured at time points up to 2 weeks following bolus exposure using optical microscopy, immunochemistry, fluorescence microscopy, and Image J image analysis software.
PEGPLA drug release rates averaged less than < 2 weeks, but were improved through incorporation of poly(lactic-co-glycolic) acid microspheres. Increased neurite extension was evidenced in both PC12 and retinal explants during the initial 1 week study, with results comparable to a positive control receiving neurotrophin directly in cell culture medium. However, in a two week study conducted with retinal explants, it was determined that drug delivery slowed and extended neurites began to retract. The use of cell adhesion molecules appeared to not only mitigate this effect, but also to promote further neurite extension, even after neurotrophin delivery from polymer hydrogels was largely complete.
Drug delivery applied to neural prostheses may induce neurite extension to electrode surfaces; however, additional modifications, such as the incorporation of cell adhesion molecules, are required to support a chronic interface between the electrode and neuron extensions.
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