In patients blinded by retinal degeneration, epiretinal prostheses aim at electrically stimulating the surviving retinal cells to restore partial sight. Recent tests in patients with epiretinal implants have revealed that electrical stimulation of the retina may result in the percept of color, depending on the frequency of stimulation. This award supported our investigation on the mechanisms of color encoding in response to electrical stimulation of the retina, which could prove pivotal for the design of advanced retinal prosthetics that elicit both percept and color. In patients with retinal prostheses, significant degradation of spatial visual information with respect to normal vision is inevitable; the addition of color vision would represent a tremendous improvement to the efficacy of current devices, providing additional visual cues to the patient.

Intellectual Merit: In this award, we have identified, for the first time, a directly applicable “amplitude-frequency” electrical stimulation strategy to “encode color” in future retinal prosthetics. Through a predictive computational platform developed in our laboratories, we have been able to identify stimulation parameters to selectively target small bistratified retinal ganglion cells (RGCs), which have been shown to contribute to “blue-yellow” color opponency in the retinal circuitry. To accomplish this, we developed biophysically and morphologically detailed models of retinal RGCs and utilized our multiscale computational platform to determine their response as a function of the stimulation frequency, up to 200 Hz. We have found that the firing rate of D1-bistratified RGCs is greater compared to A2-monostratified RGCs at high frequency, and the spiking rate observed in the A2-monostratified cell cannot follow the stimulus pulses with a similar rate. This suggested that it is possible to exploit the differential RGCs response in retinal prosthetic systems by varying stimulation frequency and controllably induce different percepts, such as color. These findings were validated in clinical testing, where studies in blind subjects affected by Retinitis Pigmentosa (RP) and fitted with an artificial retina demonstrated that color sensation could be elicited and that the colors perceived may be shifted by the stimulation frequency.

Broader Impacts: This award allowed us to assemble a highly interdisciplinary and complementary team of electrical engineers, biomedical engineers, clinicians, and neurobiologists to advance the field of retinal prostheses, which can help the 50 million patients worldwide affected by incurable retinal degeneration. This project has contributed to advance the state of predictive multiscale computational models of the retina and verified these through clinical testing. Further, this project has offered the opportunity to train students and expose them to cross-disciplinary, cross-institutional, activities that fostered the convergence of computational and experimental approaches to advance the field of retinal prosthetic systems.

Last Modified: 08/30/2021
Modified by: Gianluca Lazzi