Retinal ganglion cell (RGC) degeneration in glaucoma is both a spatial and temporal progression of physiological dysfunction. Recent studies indicate that deficits in anterograde transport in RGC axons precede their physical loss and axon conductance is compromised during this early phase of degeneration. Interestingly, these functional deficits in axon physiology tend to occur in clusters of neighboring RGCs, suggesting that external cues in the immediate milieu may play a role in spatial spreading of functional deficits. Currently the physiological relevance of spatial aspects in the glaucomatous neurodegeneration process is poorly understood because traditional assays do not have the spatiotemporal resolution to probe groups of cells throughout an intact neurodegenerative tissue. The lack of effective assays to probe groups of cells in a spatiotemporally controlled manner, while maintaining their in vivo structural and chemical relationships poses a major challenge to our understanding of neurodegeneration in a variety of diseases. To address this issue, we are developing a versatile graphene-based microfluidic platform, which allows for recording and manipulating electrical activities of individual cells in a whole retinal tissue, long term ex vivo culture of retina in god health, multiple point-access to the retina for local stimulation through chemical factors, as well as high resolution confocal microscopy examination of the retina. A unique advantage of graphene is that its whole volume is exposed to the environment, which maximizes its sensitivity to local electrochemical potential change. For example, graphene transistors are capable of detecting individual gas molecules, due to its high surface to volume ratio and high electron mobility (100 to 1000 times higher than silicon). The high electron mobility also enables graphene transistors to operate at very high frequencies (up to 500 GHz), leading to high temporal resolution. Because of its strength and flexibility, graphene can adhere to cell membranes or tissue slices to achieve high electrical sensitivity. Furthermore, a single-layer of graphene transmits more than 97% of incident light, making it ideal to be used as transparent electrical devices that are compatible with optical imaging techniques. Recently, we have shown that scanning photocurrent microscopy can provide a local photoconductance map with a precision 10 times greater than the diffraction limit. As such, our unprecedented neurotechnology, a rare combination of graphene probes, scanning photocurrent microscopy, and a novel microfluidic platform, will enable new assays to study cell-cell interactions that regulate neurodegenerative disorders of retina.
Glaucoma, a neurodegenerative disorder that targets retinal ganglion cells, is predicted to affect over 80 million people worldwide by the year 2020. How the disease spreads between cells is critical to understanding disease progression, but our understanding is hampered by a lack of tools to probe this process. This proposal seeks to create a graphene-based microfluidic platform to probe potassium homeostasis and subsequent physiological dysfunction of ganglion cells, as a potential mechanism for disease progression in glaucoma.
| Fischer, Rachel A; Zhang, Yuchen; Risner, Michael L et al. (2018) Impact of Graphene on the Efficacy of Neuron Culture Substrates. Adv Healthc Mater 7:e1701290 |
| Wang, Rui; Wang, Tianjiao; Hong, Tu et al. (2018) Probing photoresponse of aligned single-walled carbon nanotube doped ultrathin MoS2. Nanotechnology 29:345205 |
| Zhang, Yuchen; Dodson, Kirsten H; Fischer, Rachel et al. (2016) Probing electrical signals in the retina via graphene-integrated microfluidic platforms. Nanoscale 8:19043-19049 |
