Abstract
In Parkinson's disease, the degeneration of dopaminergic neurons in substantia nigra leads to a decrease in the physiological levels of dopamine in striatum. The existing dopaminergic therapies effectively alleviate the symptoms, albeit they do not revert the disease progression and result in significant adverse effects. Transplanting dopaminergic neurons derived from stem cells could restore dopamine levels without additional motor complications. However, the transplanted cells disperse in vivo and it is not possible to stimulate them on demand to modulate dopamine release to prevent dyskinesia. In order to address these issues, this paper presents a multifunctional leaky optoelectrical fiber for potential neuromodulation and as a cell substrate for application in combined optogenetic stem cell therapy. Pyrolytic carbon coated optical fibers are laser ablated to pattern micro‐optical windows to permit light leakage over a large area. The pyrolytic carbon acts as an excellent electrode for the electrochemical detection of dopamine. Human neural stem cells are genetically modified to express the light sensitive opsin channelrhodopsin‐2 and are differentiated into dopaminergic neurons on the leaky optoelectrical fiber. Finally, light leaking from the micro‐optical windows is used to stimulate the dopaminergic neurons resulting in the release of dopamine that is detected in real‐time using chronoamperometry.
Highlights
Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc)
We describe the fabrication of a LOEF, a pyrolytic carbon coated optical fiber with an array of light-emitting micro-optical windows
The 15 μm thick polyimide buffer layer on the optical fiber decomposes resulting in an ≈8 μm thick pyrolytic carbon layer surrounding the cladding (Figure 2a)
Summary
Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc). We pursue the vision of a brain bioimplant for autonomous control of dopaminergic neurons derived from optogenetic human neural stem cells for on-demand light-induced release of dopamine to restore the striatal dopamine levels (Figure 1 (left)). For this purpose, a multifunctional leaky optoelectrical fiber (LOEF) has been developed to simultaneously realize three functions: i) a substrate for the delivery of optogenetic stem cell–derived dopaminergic neurons, ii) an actuator for the optical stimulation of these dopaminergic neurons to release dopamine, and iii) an electrochemical sensor for realtime detection of the light-induced dopamine release (Figure 1 (right). The ability of the LOEF to simultaneously stimulate a large population of optogenetic dopaminergic neurons on its surface by light and subsequently detect the dopamine release was confirmed by chronoamperometry
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
