The light-dependent pseudo-capacitive charging of conjugated polymer nanoparticles coupled with the depolarization of the neuronal membrane.

The mechanism underlying visual restoration in blind animal models of retinitis pigmentosa using a liquid retina prosthesis based on semiconductive polymeric nanoparticles is still being debated. Through the application of mathematical models and specific experiments, we developed a coherent understanding of abiotic/biotic coupling, capturing the essential mechanism of photostimulation responsible for nanoparticle-induced retina activation. Our modeling is based on the solution of drift-diffusion and Poisson-Nernst-Planck models in the multi-physics neuron-cleft-nanoparticle-extracellular space domain, accounting for the electro-chemical motion of all the relevant species following photoexcitation. Modeling was coupled with electron microscopy to estimate the size of the neuron-nanoparticle cleft and electrophysiology on retina explants acutely or chronically injected with nanoparticles. Overall, we present a consistent picture of electrostatic depolarization of the bipolar cell driven by the pseudo-capacitive charging of the nanoparticle. We demonstrate that the highly resistive cleft composition, due to filling by adhesion/extracellular matrix proteins, is a crucial ingredient for establishing functional electrostatic coupling. Additionally, we show that the photo-chemical generation of reactive oxygen species (ROS) becomes relevant only at very high light intensities, far exceeding the physiological ones, in agreement with the lack of phototoxicity shown in vivo.

The role of conventional and unconventional adaptive routes in lowering of intraocular pressure: Theoretical model and simulation.

In this article, we propose a theoretical model leveraging the analogy between fluid and electric variables to investigate the relation among aqueous humor (AH) circulation and drainage and intraocular pressure (IOP), the principal established risk factor of severe neuropathologies of the optic nerve such as glaucoma. IOP is the steady-state result of the balance among AH secretion (AHs), circulation (AHc), and drainage (AHd). AHs are modeled as a given volumetric flow rate electrically corresponding to an input current source. AHc is modeled by the series of two linear hydraulic conductances (HCs) representing the posterior and anterior chambers. AHd is modeled by the parallel of three HCs: a linear HC for the conventional adaptive route (ConvAR), a nonlinear HC for the hydraulic component of the unconventional adaptive route (UncAR), and a nonlinear HC for the drug-dependent component of the UncAR. The proposed model is implemented in a computational virtual laboratory to study the value attained by the IOP under physiological and pathological conditions. Simulation results (i) confirm the conjecture that the UncAR acts as a relief valve under pathological conditions, (ii) indicate that the drug-dependent AR is the major opponent to IOP increase in the case of elevated trabecular meshwork resistance, and (iii) support the use of the model as a quantitative tool to complement in vivo studies and help design and optimize medications for ocular diseases.

A multi-scale/multi-physics model for the theoretical study of the vascular configuration of retinal capillary plexuses based on OCTA data.

The retinal tissue is highly metabolically active and is responsible for translating the visual stimuli into electrical signals to be delivered to the brain. A complex vascular structure ensures an adequate supply of blood and oxygen, which is essential for the function and survival of the retinal tissue. To date, a complete understanding of the configuration of the retinal vascular structures is still lacking. Optical coherence tomography angiography has made available a huge amount of imaging data regarding the main retinal capillary plexuses, namely the superficial capillary plexuses (SCP), intermediate capillary plexuses (ICP) and deep capillary plexuses (DCP). However, the interpretation of these data is still controversial. In particular, the question of whether the three capillary plexuses are connected in series or in parallel remains a matter of debate. In this work, we address this question by utilizing a multi-scale/multi-physics mathematical model to quantify the impact of the two hypothesized vascular configurations on retinal hemodynamics and oxygenation. The response to central retinal vein occlusion (CRVO) and intraocular pressure (IOP) elevation is also simulated depending on whether the capillary plexuses are connected in series or in parallel. The simulation results show the following: (i) in the in series configuration, the plexuses exhibit a differential response, with DCP and ICP experiencing larger pressure drops than SCP; and (ii) in the in parallel configuration, the blood flow redistributes uniformly in the three plexuses. The different vascular configurations show different responses also in terms of oxygen profiles: (i) in the in series configuration, the outer nuclear layer, outer plexiform layer and inner nuclear layer (INL) are those most affected by CRVO and IOP elevation; and (ii) in the in parallel configuration the INL and ganglion cell layer are those most affected. The in series results are consistent with studies on paracentral acute middle maculopathy, secondary to CRVO and with studies on IOP elevation, in which DCP and ICP and the retinal tissues surrounding them are those most affected by ischemia. These findings seem to suggest that the in series configuration better describes the physiology of the vascular retinal capillary network in health and disease.

Shedding Light on Thermally Induced Optocapacitance at the Organic Biointerface.

Photothermal perturbation of the cell membrane is typically achieved using transducers that convert light into thermal energy, eventually heating the cell membrane. In turn, this leads to the modulation of the membrane electrical capacitance that is assigned to a geometrical modification of the membrane structure. However, the nature of such a change is not understood. In this work, we employ an all-optical spectroscopic approach, based on the use of fluorescent probes, to monitor the membrane polarity, viscosity, and order directly in living cells under thermal excitation transduced by a photoexcited polymer film. We report two major results. First, we show that rising temperature does not just change the geometry of the membrane but indeed it affects the membrane dielectric characteristics by water penetration. Second, we find an additional effect, which is peculiar for the photoexcited semiconducting polymer film, that contributes to the system perturbation and that we tentatively assigned to the photoinduced polarization of the polymer interface.

Physics-based modeling of Age-related Macular Degeneration-A theoretical approach to quantify retinal and choroidal contributions to macular oxygenation.

We developed a mathematical model to characterize how macular oxygenation may be affected by abnormalities in the retinal and choroidal oxygen supplies. The macular region is modeled as a layered structure including: ganglion cell and nerve fiber layers, inner plexiform layer, inner nuclear layer, outer plexiform layer, outer nuclear layer, inner segment of photoreceptors layer and retinal pigmented epithelium. Each layer is characterized by specific levels of oxygen consumption. The vitreous and the choroid are located at the macula boundary and provide oxygen via boundary conditions of Dirichlet type. The three capillary plexi (superficial, intermediate, and deep) of the retinal circulation pierce the macular layers and provide oxygen via a volumetric source that depends on the retinal blood flow. Oxygen profiles through the macular tissue are calculated by simulating the balance among oxygen supply, consumption and diffusion in: (a) physiological baseline conditions; (b) retinal blood flow reduced by 10%, 30% and 50% with respect to baseline; (c) choroidal oxygen level diminished by 10%, 30% and 50% with respect to baseline. Model simulations predict that: (1) the oxygenation of the foveal avascular zone is not affected by reduction in retinal blood flow; (2) a reduction in choroidal oxygen supply significantly affects the outer layers, especially the photoreceptors and outer nuclear layers; (3) the impact of reduction in choroidal oxygen supply is larger in the region more proximal to the macular center; (4) the impact of reduction in retinal blood flow is larger in the region more proximal to the macular periphery. The proposed mathematical model suggests that changes in retinal and choroidal oxygen supplies impact the oxygenation of the macular tissue differentially. These results may help better understand the pathogenesis of macular degeneration.

Photoelectrochemistry and Drift-Diffusion Simulations in a Polythiophene Film Interfaced with an Electrolyte.

Although the efficiency of organic polymer-based retinal devices has been proved, the interpretation of the working mechanisms that grant photostimulation at the polymer/neuron interface is still a matter of debate. To contribute solving this issue, we focus here on the characterization of the interface between poly(3-hexyltiophene) films and water by the combined use of electrochemistry and mathematical modeling. Simulations well reproduce the buildup of photovoltage (zero current condition) upon illumination of the working electrode made by a polymer film deposited onto an indium tin oxide (ITO) substrate. Due to the essential unipolar transport in the photoexcited film, diffusion leads to a space charge separation that is responsible for the initial photovoltage. Later, electron transfer reactions toward oxygen in the electrolyte extract negative charge from the polymer. In spite of the simple model studied, all of these considerations shed light on the possible coupling mechanisms between the polymeric device and the living cell, supporting the hypothesis of pseudocapacitive coupling.