Functional analysis of an LGN-based visual prosthesis

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We are developing a visual prosthesis that can restore vision to the blind. Finding a treatment for blindness is significant as it is projected to impact 1 in 28 individuals over the age of 45 by the year 2030 (~3.5% of the population), including over 100,000 Veterans. Further, blindness is associated with increased levels of depression, obesity, diabetes, and accidental falls, and estimates suggest two-thirds of the blind are unemployed. Potential treatments are under development, including pharmaceutical, genetic, stem cell, optogenetic and prosthetic approaches, but almost all target the retina and thus offer little hope to a large portion of the blind population. This includes battlefield soldiers, returning from combat with bilateral traumatic eye injury, and other members of the general population with similar afflictions. It also includes those with glaucoma, age-related macular degeneration, and diabetic retinopathy, the 3 most common cause of blindness in aging Veterans (and the general population). The lateral geniculate nucleus (LGN) of the thalamus is an attractive site for implantation of a prosthesis as it is beyond the disease/trauma associated with most causes of blindness and thus a working device would offer a treatment to large portions of the blind population. In addition, the LGN is more spatially expansive than the retina and thus allows for a larger number of stimulation sites and higher acuity. At the same time, the neural signaling patterns used by LGN neurons are much less abstract than those of the visual cortex, thereby allowing for more straightforward encoding schemes (than those required by cortical prostheses). While it has been challenging to develop a high-count, multi-channel device that can safely be implanted into a deep brain structure, our colleagues have recently developed such a device and much effort is underway to advance this technology. However, little is known about how to effectively stimulate the LGN with a prosthesis and this lack of understanding will impede progress towards a clinical device. Here, we propose 4 Aims focused on learning how to effectively drive LGN neurons with a prosthesis. Our initial testing shows that stimulation from of the LGN can indeed drive downstream visual circuits and further, that primary visual cortex (V1) is activated as well (secondary to the activation of the LGN). Thus, our Aims will focus on determining how to most effectively activate the LGN and we will explore whether the same conditions that maximize LGN activation also produce robust activation of visual cortex. As part of this investigation, we will also explore whether individual cell types in LGN have different sensitivities to electric stimulation as is the case in many other regions of the CNS. This will be quite useful as the different layers of LGN are comprised of different cell types and understanding how to optimally activate each may lead to better outcomes. Finally, we will evaluate the stability of performance for implanted devices for chronic implantation. We believe that the comprehensive evaluation proposed here will provide a foundation from which to systematically advance future pre-clinical and clinical studies.