Injectable Artificial Photoreceptors: STEM Cell Functional Integration and in vivo Electrophysiological Validation in Retinal Degeneration Models
Afshin Izadian, Ali Torkashvand, Benjamin Allan McCall, Yong Gao, Christine M. Taylor, Fateme Karimi Hafshejani, Arupratan Das, Michelle L. Surma, Sunland Gong, Amir Reza HajrasoulihaIn this study, an injectable artificial photoreceptor (APR) is engineered to transduce visible light into cell‐level electrical stimulation via localized surface plasmon resonance to restore vision in patients with vision loss. APRs comprise gold nanoparticles (AuNPs) with poly (vinylidene fluoride‐co‐hexafluoropropylene) (PVDF‐HFP) dielectric coating and are integrated onto a high‐permittivity barium titanate core. This yields a stable nanocomposite with maximum absorbance in the green band at around 525 nm. APRs were evaluated in vitro using human pluripotent stem cell‐derived retinal ganglion cells (hRGCs) exposed to light stimulation. In vivo efficacy was assessed following intravitreal injection of APRs in the rd1 mouse model, and functional outcomes were evaluated using visual evoked potentials (VEPs) and pupillary light reflex (PLR) testing. In vitro, optical stimulation of hRGCs in the presence of APRs increased multielectrode‐array (MEA) firing. This shifted cellular metabolism toward mitochondrial oxidative phosphorylation without inducing apoptosis. In rd1 mice, intravitreal APR delivery produced robust restoration of light‐evoked retinal activity in explant MEAs and improved functional readouts in vivo, validated by enhanced PLR and increased N1 amplitudes on flash VEPs. This study demonstrates that a fully injectable nanophotonic prosthesis can restore light responsiveness in a retinal degeneration model without the need for implanted electronics or genetic modification.