Characterization of Induced Current Density During Transcorneal Electrical Stimulation to Promote Neuroprotection in the Degenerating Retina.

OBJECTIVE: Transcorneal electrical stimulation (TES) is a promising approach to delay retinal degeneration by inducing extracellular electric field-driven neuroprotective effects within photoreceptors. Although achieving precise electric field control is feasible in vitro, characterizing these fields becomes intricate and largely unexplored in vivo due to uneven distribution in the heterogeneous body. In this paper, we investigate and characterize electric fields within the retina during TES to assess the potential for therapeutic approaches Methods: We developed a computational model of a rat's head, enabling us to generate predictive simulations of the voltage and current density induced in the retina. Subsequently, an in vivo experimental setup involving Royal College of Surgeon (RCS) rats was implemented to measure the voltage across the retina using identical electrode configurations as employed in the simulations. RESULTS: A stimulation amplitude of 0.2-0.3 mA may be necessary during TES in rats to induce a current density of at least 20 A/[Formula: see text] in the retina, which is the lower limit for triggering neuroprotective effects according to culture studies on neural cells. Measurement taken from cadaveric pigs' eyes revealed that a stimulation amplitude of 1 mA is necessary for achieving the same current density. CONCLUSION: The computational modeling approach presented in this study was validated with experimental data and can be leveraged for predictive simulations to optimize the electrode design and stimulation parameters of TES. SIGNIFICANCE: Once validated, the flexibility and low research cost of computational models are valuable in optimization studies where testing on live subjects is not feasible.

Small-animal 360-deg fluorescence diffuse optical tomography using structural prior information from ultrasound imaging.

We demonstrate dual modality of free-space fluorescence diffuse optical tomography (FDOT) and handheld ultrasound (US) imaging to reveal both functional and structural information in small animals. FDOT is a noninvasive method for examining the fluorophore inside an object from the light distribution of the surface. In FDOT, a 660-nm continuous wave diode laser was used as an excitation source and an electron-multiplying charge-coupled device (EMCCD) was used for fluorescence data acquisition. Both the laser and EMCCD were mounted on a 360-deg rotation gantry for the transmission optical data collection. The structural information is obtained from a 6- to 17-MHz handheld US linear transducer by single-side access and conducts in the reconstruction as soft priors. The rotation ranges from 0 deg to 360 deg; different rotation degrees, object positions, and parameters were determined for comparison. Both phantom and tissue phantom results demonstrate that fluorophore distribution can be recovered accurately and quantitatively using this imaging system. Finally, an animal study confirms that the system can extract a dual-modality image, validating its feasibility for further in vivo experiments. In all experiments, the error and standard deviation decrease as the rotation degree is increased and the error was reduced to 10% when the rotation degree was increased over 135 deg.

Ultrasonic Retinal Neuromodulation and Acoustic Retinal Prosthesis.

Ultrasound is an emerging method for non-invasive neuromodulation. Studies in the past have demonstrated that ultrasound can reversibly activate and inhibit neural activities in the brain. Recent research shows the possibility of using ultrasound ranging from 0.5 to 43 MHz in acoustic frequency to activate the retinal neurons without causing detectable damages to the cells. This review recapitulates pilot studies that explored retinal responses to the ultrasound exposure, discusses the advantages and limitations of the ultrasonic stimulation, and offers an overview of engineering perspectives in developing an acoustic retinal prosthesis. For comparison, this article also presents studies in the ultrasonic stimulation of the visual cortex. Despite that, the summarized research is still in an early stage; ultrasonic retinal stimulation appears to be a viable technology that exhibits enormous therapeutic potential for non-invasive vision restoration.