Retinal stimulation strategies to restore vision: Fundamentals and systems

Abstract

Retinal degeneration, a leading cause of blindness worldwide, is primarily characterized by the dysfunctional/degenerated photoreceptors that impair the ability of the retina to detect light. Our group and others have shown that bioelectronic retinal implants restore useful visual input to those who have been blind for decades. This unprecedented approach of restoring sight demonstrates that patients can adapt to new visual input, and thereby opens up opportunities to not only improve this technology but also develop alternative retinal stimulation approaches. These future improvements or new technologies could have the potential of selectively stimulating specific cell classes in the inner retina, leading to improved visual resolution and color vision. In this review we will detail the progress of bioelectronic retinal implants and future devices in this genre as well as discuss other technologies such as optogenetics, chemical photoswitches, and ultrasound stimulation. We will discuss the principles, biological aspects, technology development, current status, clinical outcomes/prospects, and challenges for each approach. The review will cover functional imaging documented cortical responses to retinal stimulation in blind patients.

Organic Bioelectronics: Materials and Biocompatibility

“…In contrast, in vivo testing usually occurs over a longer ‘chronic’ period which may be weeks, months, or years [3,5,23]. Long-term issues and potential remedies associated with implantable devices are best studied in vivo.…”

“…Some systems are designed primarily for in vitro recording of cultured neurons, organotypic explant preparations, and acute brain and/or spinal cord sections, while others have the capacity for in vivo recordings in live animals—freely moving or anaesthetized. To maximise the spatial recording resolution of multi-electrode arrays, it is important to minimise current spread in the extracellular fluid and crosstalk between neighbouring electrodes, which is challenging given that electrical contact between electrode arrays and tissue is poor (high impedance) [3,5]. Since neurons of the same type generate identical action potentials, the only way to differentiate the activity of a single neuron is to reduce the distance and impedance between the electrode and the neuron of interest [71].…”

“…Indeed, medical electronic devices are now a mature technology. Examples include deep-brain stimulations to treat Parkinson disease [1], neural stimulation to treat epilepsy or paralysis [2], cochlear and vestibular implants for hearing and balance [3,4], and retinal prosthetic devices to treat blindness or vision loss [5]. As bioelectronics develops still further, broader applications such as controlling electrical appliances by neuronal read-out [6] become viable propositions.…”

Optogenetik als mögliche Therapie bei degenerativen Netzhauterkrankungen

“…Bei der nassen Form der AMD zum Beispiel überleben mehr als 50 % der Ganglienzellen, bei trockener AMD fast alle, selbst wenn kaum noch gesunde Photorezeptoren vorhanden sind. Bei RP überleben selbst im Spätstadium 70-80 % der Bipolarzellen und 25-40 % der Ganglienzellen [18].…”

Comparative Study of Sevoflurane and Isoflurane Anesthesia for the Long-term Safety Evaluation of Visual Prosthesis with Rabbits

“…( 1) We have been developing a suprachoroidaltransretinal-stimulation retinal prosthesis using a 49-channel electrode for clinical trial. (2) Prior to practical application in human subjects, animal experiments are necessary to prove that the prosthetic devices are functionally stable in vivo for long periods.…”