Abstract
Purpose :
Purpose: Photoreceptor loss is a culprit of blinding disorders, including macular degeneration and inherited retinal disease. Currently, there is no treatment for photoreceptor replacement therapy. Although photoreceptor loss results in the inability of the retina to form images, much of the wiring through remaining retinal ganglion cells (RGCs) is intact in these diseases. Attempts to use electrodes to stimulate the RGCs have been successful. Yet, the resolution is low and surgical implantation is challenging, limiting the widely accepted method in the clinic. Herewith, we hypothesized that gold nanoparticle (GNP) dielectric property might be used to generate the signal in RGCs.
Methods :
Methods: Monodisperse GNP with citrate coating was generated using modified Turkevich and Frens methods. PVDF coating was performed using the PVP linkage between GNP and PVDF. Polymer coating was confirmed with Scanning Electron Microscope and Dynamic Light Scattering. Electrical assay of Human stem-cell-derived retinal ganglion cells was assessed in the presence of different concentrations of GNP and PVDF-coated GNP by multi-electrode array (MEA). Blind rd1 mutant mice in C57BL/6j background were purchased from Jackson and were used for intravitreal injection experiments. Nanoparticle and polymer-coated nanoparticles in a total volume of 1 µl per injection were injected in both WT and rd1 KO mice. Fundus imaging and optical coherence tomography (OCT) followed by electroretinogram (ERG) were performed in WT and rd1 KO mice at different time points following intravitreal injections.
Results :
Gold nanoparticle size was averaged at 20nm as measured by SEM. The UV-Vis spectrophotometry confirmed the pick of plasmon resonance at 524nm. The MEA showed a substantial and increased number of spikes in the human stem cell-derived RGCs corresponding to frequencies and intensities of light, with the most cell activity in the presence of polymer-coated gold nanoparticles. The optical coherence tomography confirmed the presence of GNP up to 72 hours post intravitreal injection in the vitreous cavity. The ERG was recovered in rd1 blind mice receiving polymer-coated GNP and not in the GNP-only group.
Conclusions :
Polymer-coated GNP has the potential to be used as a photoreceptor substitute therapy in degenerative retinal disease.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.