Abstract:
Retinal degenerative diseases that progressively lead to severe blindness impact the affected individual’s quality-of-life. Visual prosthesis technology aims to provide an individual a potential means of obtaining visual information lost to them by blindness. Since the proof-of-concept success in 1968 of a device implanted in a human, visual prostheses have had sustained academic research and commercial interest. However, commercial failure of two retinal prosthesis device has raised concerns for the visual prosthesis field. To learn from this experience, research in this dissertation is aimed at understanding the impact of electric stimulation on the target neural tissue and investigating technology for a visual cortex prosthesis, which can reach a larger patient population (compared to a retinal prosthesis).

My first set of experiments assessed, in an animal model of retinal degeneration, the condition of the brain and its ability to receive artificial vision information. Retinitis Pigmentosa has been proven to impact the human brain. My study investigated the extent to which this was replicated in a rat animal model of a single genetic mutation of Retinitis Pigmentosa. The P23H-1 rat was investigated with electrophysiology and immunohistochemistry to understand the brain’s function and structural condition. The rat brain’s response to light and electric stimulation was investigated, and the change of visually evoked responses and maintenance of electrically evoked responses was observed. Histology images show a relatively stable macrostructure of the blind rat brain.

I also performed retinal and cortical implant procedures to test newly developed visual prosthesis technology to enable investigations into researching neural change occurring from blindness and electric stimulation. A retinal device with Parylene-C as its main component was tested and its feasibility in the small eye of a rat animal model was investigated. The device can survive 4-weeks of implantation and is stable within the eye. In support of the development of a novel cortical visual prosthesis device that fits the need of blind individuals, I used a small animal model first to prove the efficacy and safety of a novel neurostimulation electrode. The device, named StiMote, is in preclinical development. I worked to characterize the full ability of the neural interface, High-Density Carbon Fibers with electrodeposited Platinum-Iridium. The ability of PtIr-HDCF as a recording and stimulation neural interface device was verified using electrochemical measurements before, during, and after a long-duration 7-hour electric stimulation session that simulates a full day of device use.

PtIr-HDCF as a neural interface device was verified by my previous work and its improvement in reducing neuroinflammatory response compared to other microelectrode array archetypes has been previously researched. As a result, PtIr-HDCF can be used as a device to monitor the brain and can better extract the effect of electric stimulation on the brain alone. I recorded neural electrophysiology to verify the rat brain’s sensitivity to stimuli before and after 7-hour stimulation. To supplement the already existing neural implant and electric stimulation inflammation data, Spatial Transcriptomics as a novel method to define electric stimulation safety was performed. Spatial Transcriptomics showed that PtIr-HDCF, when compared to a conventional microwire array, performs better in sustaining neural health by reducing neuroinflammation and eliciting mRNA upregulation of neurotrophic factors.

Findings of this project can be used to better inform future investigations into brain electrophysiology and transcriptomics projects aimed to understand the neural change from blindness and electric stimulation.

Committee Chair(s): Dr. James Weiland

Location: 1501 Auditorium, NCRC Bldg 32 & https://umich.zoom.us/j/91500987159?pwd=RWIvQkZVT2FHZjQ2S1BBS2k0ck1SUT09