Advancing the Retina Implant: Exploring the separation of ON and OFF responses in normal and degenerated mouse retina stimulated electrically with the subretinal implant Alpha AMS.

• Applicant: Dr. Zohreh Hosseinzadeh, Ph.D.
• Subject Area: Ophthalmology ; Anatomy and Physiology
• Term: from 2018 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 398118700

Worldwide over 8 million people suffer from retinitis pigmentosa and macular degeneration, which lead to loss of photoreceptor function and blindness. Electronic retinal implants have been developed in order to restore the visual function in these patients. The Alpha AMS implant developed in Tübingen has shown the best patient performance of any implant, however, patient performance still falls short of the widely accepted threshold for blindness of 20/200. One possibility for improvement is to selectively activate the ON and OFF information channels of the eye. Therefore, the main goal of the project will be to study selective electrical activation of defined retinal ganglion cell (RGC) types by the Alpha AMS implant chip. In Work Package 1 (WP1), we will test amplitude-modulated electrical pulse trains for differential activation of the ON and OFF pathways. In WP2, we will vary pulse train frequency (without amplitude modulation) for differential activation. Such activation will be examined in both blind and healthy mouse retina using a microelectrode array (MEA) to stimulate epi- and subretinally. While the MEA will be used to record the action potentials of RGCs during epiretinal stimulation, sharp microwire, flexible MEA, and patch electrodes will be used to record during subretinal stimulation. To explore signalling within network-mediated RGC responses, pharmacological inhibitors will be applied. To characterize the stimulated ON and OFF RGCs, visual stimulation, presynaptic currents, and morphological classification will be used. Finally in WP3, stimuli proven to selectively activate ON and OFF RGCs will be generated in the Alpha AMS chip through modulation of light patterns. Recording from blind mouse retina mounted on the chip, it is our final goal to show selective activation of ON and OFF RGC types. Eventually, by proving that pathway-specific activation via the implant is possible, we hope to foster the development of new retinal implants that integrate the natural visual coding used in healthy eyes.

• DFG Programme: Research Grants