June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
The role of oxygen in the photoactivation of organic retinal protheses
Author Affiliations & Notes
  • Greta Chiaravalli
    Physics, Politecnico di Milano, Milano, Lombardia, Italy
    Istituto Italiano di Tecnologia Center for Nano Science and Technology, Milano, Lombardia, Italy
  • Riccardo Sacco
    Mathematics, Politecnico di Milano, Milano, Lombardia, Italy
  • Guglielmo Lanzani
    Istituto Italiano di Tecnologia Center for Nano Science and Technology, Milano, Lombardia, Italy
    Physics, Politecnico di Milano, Milano, Lombardia, Italy
  • Footnotes
    Commercial Relationships   Greta Chiaravalli None; Riccardo Sacco None; Guglielmo Lanzani None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 4534 – F0321. doi:
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    • Get Citation

      Greta Chiaravalli, Riccardo Sacco, Guglielmo Lanzani; The role of oxygen in the photoactivation of organic retinal protheses. Invest. Ophthalmol. Vis. Sci. 2022;63(7):4534 – F0321.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : In 2020 the injection of Poly(3-hexylthiophene-2,5-diyl) (P3HT) nanoparticles (NPs) in retinitis pigmentosa model rats has proved to treat degenerative blindness (Maya-Vetencourt et al. 2020). Despite the effectiveness of this approach, the working principles are still matter of debate and any experimental investigation has not led to a conclusive interpretation. In this work we address the theoretical study of the interaction among the P3HT-NPs, the retinal electrolytic environment and a neuron membrane, aiming at highlighting the main working principles of such a complex system

Methods : The model takes into account 3 main blocks, shown in Fig.1: (1) model of photoactivation and transport phenomena in the bulk of NP (2) study of redox and capacitive phenomena at the NP-retinal oxygenated electrolyte interface, where superoxide O2- anion is produced;(3) model of neuron interaction with the NP-modified electrolytic environment. The description is performed through the Drift-Diffusion and Poisson-Nernst-Planck equations. Model calibration has been performed through electrochemical experiments of P3HT in oxygenated environment.

Results : Fig.2 shows neuron depolarization(left) and superoxide concentration cO2-(right) as a function of oxygen partial pressure (Panel A) for two values of cleft thickness(10 and 100 nm) and as a function of the cleft thickness(Panel B). Predicted curve behaviors indicate that neuron depolarization and cO2- production are strongly coupled mechanisms: as O2- is formed, it accumulates in the cleft region, inducing a significant neuron depolarization which may trigger action potential firing. As the cleft increases(Panel b), the superoxide is able to redistribute and the depolarization decreases

Conclusions : The proposed theoretical model has been used as a virtual laboratory to investigate biophysical mechanisms which are hardly accessible with experiments. Model predictions seem to suggest a correlation between the presence of superoxide ion and retinal neuron depolarization and highlight the crucial role played by the molecular oxygen and by the cleft size, thus helping shed light on the controversial working principles of the retinal prosthesis

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

 

Conceptual scheme of NP-neuron interaction

Conceptual scheme of NP-neuron interaction

 

The incremental variation of neuron membrane potential (A-left, B-blue) and the O2- concentration in cleft region (A-right, B-orange) are reported as function of oxygen pressure (Panel A) and of cleft size (Panel B)

The incremental variation of neuron membrane potential (A-left, B-blue) and the O2- concentration in cleft region (A-right, B-orange) are reported as function of oxygen pressure (Panel A) and of cleft size (Panel B)

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