Ambient Light Rejection Integrated Circuit for Autonomous Adaptation on a Sub-retinal Prosthetic System

This paper introduces an ambient light rejection (ALR) circuit for the autonomous adaptation of a subretinal implant system. The sub-retinal implants, located beneath a bipolar cell layer, are known to have a significant advantage in spatial resolution by integrating more than a thousand pixels, compared to epi-retinal implants. However, challenges remain regarding current dispersion in high-density retinal implants, and ambient light induces pixel saturation. Thus, the technical issues of ambient light associated with a conventional image processing technique, which lead to high power consumption and area occupation, are still unresolved. Thus, it is necessary to develop a novel image-processing unit to handle ambient light, considering constraints related to power and area. In this paper, we present an ALR circuit as an image-processing unit for sub-retinal implants. We first introduced an ALR algorithm to reduce the ambient light in conventional retinal implants; next, we implemented the ALR algorithm as an application-specific integrated chip (ASIC). The ALR circuit was fabricated using a standard 0.35-μm CMOS process along with an image-sensor-based stimulator, a sensor pixel, and digital blocks. As experimental results, the ALR circuit occupies an area of 190 µm2, consumes a power of 3.2 mW and shows a maximum response time of 1.6 sec at a light intensity of 20,000 lux. The proposed ALR circuit also has a pixel loss rate of 0.3%. The experimental results show that the ALR circuit leads to a sensor pixel (SP) being autonomously adjusted, depending on the light intensity.

The Rules of Pulsatile Neurostimulation

Electrical stimulation of neural responses is used both scientifically in brain mapping studies and in many clinical applications such as cochlear, vestibular, and retinal implants. Due to safety considerations, stimulation of the nervous system is restricted to short biphasic pulses. Despite decades of research and development, neural implants are far from optimal in their ability to restore function and lead to varying improvements in patients. In this study, we provide an explanation for how pulsatile stimulation affects individual neurons and therefore leads to variability in restoration of neural responses. The explanation is grounded in the physiological response of channels in the axon and represented with mathematical rules that predict firing rate as a function of pulse rate, pulse amplitude, and spontaneous activity. We validate these rules by showing that they predict recorded vestibular afferent responses in macaques and discuss their implications for designing clinical stimulation paradigms and electrical stimulation-based experiments.

RETINITIS PIGMENTOSA AND ITS AYURVEDIC MANAGEMENT

Retinitis pigmentosa (RP) is a group of diseases involving progressive degeneration of photoreceptor cells of retina. Usually, it starts in mid periphery and advancing towards the macula and fovea centralis. Visual symptoms are nyctalopia (night blindness), tubular vision and reduced visual field. Symptoms of RP mostly starts on early teen age and sever visual loss occurs at ages of 40 to 50 years. RP has worldwide prevalence of 1:3000 to 1:7000 people. Males are more affected than female in ratio of 3:2. Nakulandhya and Shleshmavidagdha Drishti explained under Drishtigata Roga in Ayurvedic literature. These two are described as Sannipataja Syadhi and Kaphaj Vyadhi respectively. They have close resemblance with retinitis pigmentosa in their symptomatology. In current era treatment for RP includes Gene therapy, retinal implants, Neurotrophic factor, stem cells, retinal transplants. But these treatment options are not specific and satisfactory and expensive. All these treatments are still in their early stages of research and development. Ayurvedic Panchakarma therapies and Kriyakalpa therapies can help to regulate vitiated Doshas and provide nourishment and strength to ocular tissue. These therapies can help to maintain the existing vision of patient and reduce progression of RP.

The Body’s Cellular and Molecular Response to Protein-Coated Medical Device Implants: A Review Focused on Fibronectin and BMP Proteins

Recent years have seen a marked rise in implantation into the body of a great variety of devices: hip, knee, and shoulder replacements, pacemakers, meshes, glucose sensors, and many others. Cochlear and retinal implants are being developed to restore hearing and sight. After surgery to implant a device, adjacent cells interact with the implant and release molecular signals that result in attraction, infiltration of the tissue, and attachment to the implant of various cell types including monocytes, macrophages, and platelets. These cells release additional signaling molecules (chemokines and cytokines) that recruit tissue repair cells to the device site. Some implants fail and require additional revision surgery that is traumatic for the patient and expensive for the payer. This review examines the literature for evidence to support the possibility that fibronectins and BMPs could be coated on the implants as part of the manufacturing process so that the proteins could be released into the tissue surrounding the implant and improve the rate of successful implantation.

Editorial for the Special Issue on Micro/Nanofabrication for Retinal Implants

The retinal prosthetic community has witnessed tremendous technological advances during the last two decades since the emergence of pioneering work [...]

Two mathematical frameworks for vesicle release from a ribbon synapse of a retinal bipolar cell

Background: Bipolar cells communicate with amacrine and ganglion cells of the retina via both transient and sustained neurotransmitter release in ribbon synapses. Reconstructing the published quantitative release data from electrical soma stimulation (voltage clamp experiments) of rat rod bipolar cells were used to develop two simple models to predict the number of released vesicles as time series. In the experiment, the currents coming to the AII amacrine cell originating from releasing vesicles from the rod bipolar cell were recorded using paired-recordings in whole-cell voltage-clamp method. One of the models is based directly on terminal transmembrane voltage, so-called ‘modelV’, whereas the temporally exacter modelCa includes changes of intracellular calcium concentrations at terminals. Results: The intracellular calcium concentration method replicates a 0.43-ms signal delay for the transient release to pulsatile stimulation as a consequence of calcium channel dynamics in the presynaptic membrane, while the modelV has no signal delay. Both models produce the quite similar results in low stimuli amplitudes. However, for large stimulation intensities that may be done during extracellular stimulations in retinal implants, the modelCa predicts that the reversal potential of calcium limits the number of transiently released vesicles. Adding sodium and potassium ion channels to the axon of the cell enable to study the impact of spikes on the transient release in BC ribbons. A spike elicited by somatic stimulation causes the rapid release of all vesicles that are available for transient release, while a non-spiking BC with a similar morphometry needs stronger stimuli for any transient vesicle release. During extracellular stimulation, there was almost no difference in transient release between the active and passive cells because in both cases the terminal membrane of the cell senses the same potentials originating from the microelectrode. An exception was found for long pulses when the spike has the possibility to generate a higher terminal voltage than the passive cell. Simulated periodic 5 Hz stimulation showed a reduced transient release of 3 vesicles per stimulus, which is a recovery effect. Conclusions: We presented two mathematical concepts for vesicle release in ribbon synapses and explained decreasing efficiency in retinal implants for suprathreshold stimulation.

Model-Based Recommendations for Optimal Surgical Placement of Epiretinal Implants

A major limitation of current electronic retinal implants is that in addition to stimulating the intended retinal ganglion cells, they also stimulate passing axon fibers, producing perceptual ‘streaks’ that limit the quality of the generated visual experience. Recent evidence suggests a dependence between the shape of the elicited visual percept and the retinal location of the stimulating electrode. However, this knowledge has yet to be incorporated into the surgical placement of retinal implants. Here we systematically explored the space of possible implant configurations to make recommendations for optimal intraocular positioning of the electrode array. Using a psychophysically validated computational model, we demonstrate that better implant placement has the potential to reduce the spatial extent of axonal activation in existing implant users by up to ∼55 %. Importantly, the best implant location, as inferred from a population of simulated virtual patients, is both surgically feasible and is relatively stable across individuals. This study is a first step towards the use of computer simulations in patient-specific planning of retinal implant surgery.