Cortical Interactions between Prosthetic and Natural Vision

Arens-Arad, Tamar; Farah, Nairouz; Lender, Rivkah; Moshkovitz, Avital; Flores, Thomas; Palanker, Daniel; Mandel, Yossi

doi:10.1016/j.cub.2019.11.028

Cited by 12 publications

(14 citation statements)

References 41 publications

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“… 14 , 15 , 18 , 26 , 27 Moreover, specific cortical responses were recorded following the activation of RGCs by photovoltaic subretinal implants in rats. 28 A recent study on primates fitted with subretinal implants showed that these prostheses induced some behavioral responses. 2 However, to our knowledge, no study to date has demonstrated the transmission of information to higher visual areas following activation of the optogenetically transduced retina in primates.…”

Section: Introductionmentioning

confidence: 99%

In vivo optogenetic stimulation of the primate retina activates the visual cortex after long-term transduction

Chaffiol

Provansal

Joffrois

et al. 2022

Molecular Therapy - Methods & Clinical Development

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Over the last 15 years, optogenetics has changed fundamental research in neuroscience and is now reaching toward therapeutic applications. Vision restoration strategies using optogenetics are now at the forefront of these new clinical opportunities. But applications to human patients suffering from retinal diseases leading to blindness raise important concerns on the long-term functional expression of optogenes and the efficient signal transmission to higher visual centers. Here, we demonstrate in non-human primates continued expression and functionality at the retina level ∼20 months after delivery of our construct. We also performed in vivo recordings of visually evoked potentials in the primary visual cortex of anesthetized animals. Using synaptic blockers, we isolated the in vivo cortical activation resulting from the direct optogenetic stimulation of primate retina. In conclusion, our work indicates long-term transgene expression and transmission of the signal generated in the macaque retina to the visual cortex, two important features for future clinical applications.

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Section: Introductionmentioning

confidence: 99%

In vivo optogenetic stimulation of the primate retina activates the visual cortex after long-term transduction

Chaffiol

Provansal

Joffrois

et al. 2022

Molecular Therapy - Methods & Clinical Development

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“…Thus, visual information arising from both the peripheral normal retina and from prosthetic stimulation might interact with each other at both the retinal and the visual cortex levels, similarly to natural vision. In a previous study [12] we showed that when prosthetic natural stimuli are presented simultaneously on the retina, the information interacts at the visual cortex level, preserving known visual information processing such as lateral interactions. Another potential interaction could occur during sensory adaptation to ambient lighting, which is an important characteristic of the visual system, enabling it to function in ambient light luminance levels ranging over several orders of magnitude [13].…”

Section: Introductionmentioning

confidence: 94%

Cortical responses to prosthetic retinal stimulation are significantly affected by the light-adaptive state of the surrounding normal retina

et al. 2021

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Objective. Restoration of central vision loss in patients with age-related macular degeneration (AMD) by implanting a retinal prosthesis is associated with an intriguing situation wherein the central prosthetic vision co-exists with natural normal vision. Of major interest are the interactions between the prosthetic and natural vision. Here we studied the effect of the light-adaptive state of the normal retina on the electrical visual evoked potentials (VEPs) arising from the retinal prosthesis. Approach. We recorded electrical VEP elicited by prosthetic retinal stimulation in wild-type rats implanted with a 1 mm photovoltaic subretinal array. Cortical responses were recorded following overnight dark adaption and compared to those recorded following bleaching of the retina by light (520 nm) at various intensities and durations. Main results. Compared to dark-adapted responses, bleaching induced a 2-fold decrease in the prosthetic cortical response, which returned to the dark-adapted baseline within 30 min to several hours, depending on the degree of bleaching. This reduction was neither observed in Royal College of Surgeons (RCS) rats with a degenerated photoreceptor layer nor following intravitreal injection of a GABAa receptor blocker (bicuculine), suggesting the involvement of photoreceptors and a GABAa-mediated mechanism. Significance. These findings show a robust effect of the retinal light-adaptive state on the obtained prosthetic responses. If a similar effect is found in humans, this will have immediate implications on the design of prosthetic devices, where both natural and prosthetic vision co-exist, such as in AMD patients receiving a photovoltaic retinal implant. Similarly, standardization of the retinal light-adaptive state in prosthetic clinical trials should be considered.

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“…Long Evans pigmented rats (12 weeks old) were anesthetized with an IM injection of Xylazine (6 mg/kg), ketamine (100 mg/kg), and atropine (0.06 mg) with the addition of a topical application of Lidocain 2%; the device was implanted in the subretinal space of the rats and was monitored for over a month using a method previously reported by our group (49). Brie y, Optical coherence tomography (OCT) and fundus camera (Micron IV, Phoenix Research Laboratories, Pleasanton, CA, USA) imaging were utilized for investigating the anatomical integration of the implant with the host retina, similar to our previous reports (49)(50)(51)(52)(53).…”

Section: In-vivo and Histological Studies Of The Implant Integration ...mentioning

confidence: 99%

Fabrication of a 3D high-resolution implant for neural stimulation - challenges and solutions

Shpun

Farah

Chemla

et al. 2022

Preprint

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Background - Tissue-integrated micro-electronic devices for neural stimulation hold a great potential in restoring the functionality of degenerated organs, specifically, retinal prostheses, which are aimed at vision restoration. The fabrication process of 3D polymer-metal devices with high resolution and a high aspect-ratio (AR) is very complex and faces many challenges that impair its functionality. Approach - Here we describe the optimization of the fabrication process of a bio-functionalized 3D high-resolution 1mm circular subretinal implant composed of SU-8 polymer integrated with dense gold microelectrodes (23µm pitch) passivated with 3D micro-well-like structures (20µm diameter, 3µm resolution). To this end, a nickel (Ni) evaporated silicon (Si) wafer was sequentially spin-coated with SU-8 and photolithographed layer-by-layer, with a sharp electrode formation achieved through a two-step bi-layer lift-off process using LOR/AZ, followed by Cr/Au thin-layer sputter deposition to increase the adhesion. Next, the device was released by overnight Ni wet-etching using nitric acid, after which it was bio-functionalized with N2 plasma treatment and the addition of the bio-adhesion molecule arginine-glycine-aspartic acid (RGD). Main results - In-vitro and in-vivo investigations, including SEM and FIB cross section examinations, revealed a good structural design, as well as a good integration of the device in the rat sub-retinal space and cell migration into the wells. The reported process and optimization steps described here in detail can aid in the design and fabrication of similar neural implants. Conclusions - The reported process and optimization steps described here in detail can aid in the design and fabrication of retinal prosthetic devices or similar neural implants.

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Cortical Interactions between Prosthetic and Natural Vision

Cited by 12 publications

References 41 publications

In vivo optogenetic stimulation of the primate retina activates the visual cortex after long-term transduction

In vivo optogenetic stimulation of the primate retina activates the visual cortex after long-term transduction

Cortical responses to prosthetic retinal stimulation are significantly affected by the light-adaptive state of the surrounding normal retina

Fabrication of a 3D high-resolution implant for neural stimulation - challenges and solutions

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