PurposeExtraocular electrical stimulation is known to provide neuroprotection for retinal cells in retinal and optic nerve diseases. Currently, the treatment approach requires patients to set up extraocular electrodes and stimulate potentially weekly due to the lack of an implantable stimulation device. Hence, a minimally-invasive implant was developed to provide chronic electrical stimulation to the retina, potentially improving patient compliance for long-term use. The aim of the present study was to determine the surgical and stimulation safety of this novel device designed for neuroprotective stimulation.MethodsEight normally sighted adult feline subjects were monocularly implanted in the suprachoroidal space in the peripheral retina for 9–39 weeks. Charge balanced, biphasic, current pulses (100 μA, 500 µs pulse width and 50 pulses/s) were delivered continuously to platinum electrodes for 3–34 weeks. Electrode impedances were measured hourly. Retinal structure and function were assessed at 1-, 2-, 4-, 6- and 8-month using electroretinography, optical coherence tomography and fundus photography. Retina and fibrotic thickness were measured from histological sections. Randomized, blinded histopathological assessments of stimulated and non-stimulated retina were performed.ResultsAll subjects tolerated the surgical and stimulation procedure with no evidence of discomfort or unexpected adverse outcomes. The device position was stable after a post-surgery settling period. Median electrode impedance remained within a consistent range (5–10 kΩ) over time. There was no change in retinal thickness or function relative to baseline and fellow eyes. Fibrotic capsule thickness was equivalent between stimulated and non-stimulated tissue and helps to hold the device in place. There was no scarring, insertion trauma, necrosis, retinal damage or fibroblastic response in any retinal samples from implanted eyes, whilst 19% had a minimal histiocytic response, 19% had minimal to mild acute inflammation and 28% had minimal to mild chronic inflammation.ConclusionChronic suprathreshold electrical stimulation of the retina using a minimally invasive device evoked a mild tissue response and no adverse clinical findings. Peripheral suprachoroidal electrical stimulation with an implanted device could potentially be an alternative approach to transcorneal electrical stimulation for delivering neuroprotective stimulation.

For individuals with severe to profound hearing loss resulting from irreversibly damaged hair cells, cochlear implants can be used to restore hearing by delivering electrical stimulation directly to the spiral ganglion neurons. However, current spread lowers the spatial resolution of neural activation. Since light can be easily confined, optogenetics is a technique that has the potential to improve the precision of neural activation, whereby visible light is used to stimulate neurons that are modified with light-sensitive opsins. This study compares the spread of neural activity across the inferior colliculus of the auditory midbrain during electrical and optical stimulation in the cochlea of acutely deafened mice with opsin-modified spiral ganglion neurons (H134R variant of the channelrhodopsin-2). Monopolar electrical stimulation was delivered via each of four 0.2 mm wide platinum electrode rings at 0.6 mm centre-to-centre spacing, whereas 453 nm wavelength light was delivered via each of five 0.22 × 0.27 mm micro-light emitting diodes (LEDs) at 0.52 mm centre-to-centre spacing. Channel interactions were also quantified by threshold changes during simultaneous stimulation by pairs of electrodes or micro-LEDs at different distances between the electrodes (0.6, 1.2 and 1.8 mm) or micro-LEDs (0.52, 1.04, 1.56 and 2.08 mm). The spread of activation resulting from single channel optical stimulation was approximately half that of monopolar electrical stimulation as measured at two levels of discrimination above threshold (p<0.001), whereas there was no significant difference between optical stimulation in opsin-modified deafened mice and pure tone acoustic stimulation in normal-hearing mice. During simultaneous micro-LED stimulation, there were minimal channel interactions for all micro-LED spacings tested. For neighbouring micro-LEDs/electrodes, the relative influence on threshold was 13-fold less for optical stimulation compared electrical stimulation (p<0.05). The outcomes of this study show that the higher spatial precision of optogenetic stimulation results in reduced channel interaction compared to electrical stimulation, which could increase the number of independent channels in a cochlear implant. Increased spatial resolution and the ability to activate more than one channel simultaneously could lead to better speech perception in cochlear implant recipients.

Ulcerative colitis is a chronic disease in which the mucosa of the colon or rectum becomes inflamed. An objective biomarker of inflammation will provide quantitative measures to support qualitative assessment during an endoscopic examination. Previous studies show that transmural electrical impedance is a quantifiable biomarker of inflammation. Here, we hypothesize that impedance detects spatially restricted areas of inflammation, thereby allowing the distinction between regions that differ in their severity of inflammation. A platinum ball electrode was placed into minimally inflamed (i.e. normal) or 2,4,6-trinitrobenzene sulphonic acid (TNBS)-inflamed colonic regions of rats and impedance measurements obtained by passing current between the intraluminal and subcutaneous return electrode. Histology of the colon was correlated with impedance measurements. The impedance of minimally inflamed (normal) tissue was 1.5–1.9 kΩ. Following TNBS injection, impedance significantly decreased within the inflammatory penumbra ( p < 0.05), and decreased more in the inflammatory epicentre ( p = 0.02). Histological damage correlated with impedance values ( p < 0.05). Thus, impedance values of 1.5–1.9, 1.3–1.4 and 0.9–1.1 kΩ corresponded to minimally inflamed, mildly inflamed and moderately inflamed tissue, respectively. In conclusion, transmural impedance is an objective, spatially localized biomarker of mucosal integrity, and distinguishes between severities of intestinal inflammation.

Aim: Electrical stimulation of the left cervical vagus nerve is a feasible therapy for inflammatory bowel disease (IBD). However, due to the location of the electrode placement, stimulation is often associated with side effects. Methods: We developed a cuff electrode array, designed to be implanted onto the vagus nerve of the lower thorax or abdomen, below branches to vital organs, to minimize off-target effects to stimulation. Results: Following chronic implantation and electrical stimulation, electrodes remained functional and neural thresholds stable, while there were minimal off-target affects to stimulation. No nerve damage or corrosion of stimulated electrodes was observed. Conclusion: This novel electrode array, located on the vagus nerve below branches to vital organs, is a safe approach for the treatment of inflammatory bowel disease.