Postdoc research fellow, UNSW
The estimated number of people with blindness due to age-related macular degeneration (AMD) was 24,200 in Australia in 2004. This number has risen to a range between 39,000 and 73,000 in 2010. The prevalence of retinitis pigmentosa (RP) is about 1 in 4000 world-wide. This corresponds to 1.75 million patients with RP. As our population grows and ages, more people will be stricken by the two retinal diseases. The improvement of visual prosthesis will encourage the implant of bionic eye and help alleviate the financial burden for the diseases. The 'bionic eye' aim to restore patterned vision to those with vision loss by electrically stimulating the remaining neurons in the degenerate retina. Human trials have demonstrated the ability of these devices to elicit visual percepts or so-called phosphenes. The holy grail of bionic eye research as a means of treating profound vision loss is the capacity to exactly reproduce the same neural signals that travel between the eye and the brain during normal visual function. The visual system primarily ’sees’ the world by way of sending signals to the brain that indicate transitions from 'light ON to light OFF' and from 'light OFF to light ON' wherever an edge exists. When someone loses visual function through diseases such as retinitis pigmentosa (RP) and AMD, they lose the neural connections that make this process possible. While neural prostheses have been implanted in humans for tens of decades, the mechanisms underlying the responses of neurons to extracellular electrical stimulation are not well understood nor easily achieved. The current state-of-the-art devices can only stimulate both the ‘ON’ and ‘OFF’ pathways simultaneously, that is with no discrimination, sending confusing signals to the brain for interpretation. We are exploring new approaches to electrically stimulate the surviving neural cells in the retina using high frequency electrical stimulation, through a broad research approach comprising experimental recordings in cells of the retina combined with computational modelling. In particular, we aim to target specific information streams within the retina, such as the ‘ON’ and ‘OFF’ pathways, through selective excitation of the corresponding retinal ganglion cells (RGCs). This could deliver more natural visual perception through a bionic eye, and enable the visually impaired to regain even more of their vision after the progression of retinal disorders.
Abstract: In an effort to restore functional form vision, epiretinal prostheses that elicit percepts by directly stimulating remaining retinal circuitry were implanted in human subjects with advanced retinitis pigmentosa RP). In this study, manipulating pulse train frequency and amplitude had different effects on the size and brightness of phosphene appearance.Experiments were performed on a single subject with severe RP (implanted with a 16-channel epiretinal prosthesis in 2004) on nine individual electrodes. Psychophysical techniques were used to measure both the brightness and size of phosphenes when the biphasic pulse train was varied by either modulating the current amplitude (with constant frequency) or the stimulating frequency (with constant current amplitude).Increasing stimulation frequency always increased brightness, while having a smaller effect on the size of elicited phosphenes. In contrast, increasing stimulation amplitude generally increased both the size and brightness of phosphenes. These experimental findings can be explained by using a simple computational model based on previous psychophysical work and the expected spatial spread of current from a disc electrode.Given that amplitude and frequency have separable effects on percept size, these findings suggest that frequency modulation improves the encoding of a wide range of brightness levels without a loss of spatial resolution. Future retinal prosthesis designs could benefit from having the flexibility to manipulate pulse train amplitude and frequency independently (clinicaltrials.gov number, NCT00279500).
Pub.: 24 Nov '11, Pinned: 24 Aug '17
Abstract: Retinal ganglion cells (RGCs) demonstrate a large range of variation in their ionic channel properties and morphologies. Cell-specific properties are responsible for the unique way RGCs process synaptic inputs, as well as artificial electrical signals such as that from a visual prosthesis. A cell-specific computational modelling approach allows us to examine the functional significance of regional membrane channel expression and cell morphology.In this study, an existing RGC ionic model was extended by including a hyperpolarization activated non-selective cationic current as well as a T-type calcium current identified in recent experimental findings. Biophysically-defined model parameters were simultaneously optimized against multiple experimental recordings from ON and OFF RGCs.With well-defined cell-specific model parameters and the incorporation of detailed cell morphologies, these models were able to closely reconstruct and predict ON and OFF RGC response properties recorded experimentally.The resulting models were used to study the contribution of different ion channel properties and spatial structure of neurons to RGC activation. The techniques of this study are generally applicable to other excitable cell models, increasing the utility of theoretical models in accurately predicting the response of real biological neurons.
Pub.: 26 Feb '16, Pinned: 24 Aug '17
Abstract: In this study, ON and OFF retinal ganglion cell (RGC) models based on accurate biophysics and realistic representations of cell morphologies were used to understand how these cells selectively respond to high-frequency electrical stimulation (HFS). With optimized model parameters and the incorporation of detailed cell morphologies, these two models were able to closely replicate experimental ON and OFF RGC responses to epiretinal electrical stimulation. This modeling approach can be used to design electrical stimulus profiles capable of cell-specific activation, and is broadly applicable for the development of sophisticated stimulation strategies for visual prostheses.
Pub.: 09 Jan '15, Pinned: 24 Aug '17
Abstract: Retinal electrostimulation is promising a successful therapy to restore functional vision. However, a narrow stimulating current range exists between retinal neuron excitation and inhibition which may lead to misperformance of visual prostheses. As the conveyance of representation of complex visual scenes may require neighbouring electrodes to be activated simultaneously, electric field summation may contribute to reach this inhibitory threshold. This study used three approaches to assess the implications of relatively high stimulating conditions in visual prostheses: (1) in vivo, using a suprachoroidal prosthesis implanted in a feline model, (2) in vitro through electrostimulation of murine retinal preparations, and (3) in silico by computing the response of a population of retinal ganglion cells. Inhibitory stimulating conditions led to diminished cortical activity in the cat. Stimulus-response relationships showed non-monotonic profiles to increasing stimulating current. This was observed in vitro and in silico as the combined response of groups of neurons (close to the stimulating electrode) being inhibited at certain stimulating amplitudes, whilst other groups (far from the stimulating electrode) being recruited. These findings may explain the halo-like phosphene shapes reported in clinical trials and suggest that simultaneous stimulation in retinal prostheses is limited by the inhibitory threshold of the retinal ganglion cells.
Pub.: 18 Feb '17, Pinned: 24 Aug '17