Abstract
Purpose :
Retinitis pigmentosa and age-related macular degeneration are typical retinal diseases resulting in irreversible photoreceptor degeneration and blindness. Current clinical studies revealed the feasibility of electrical retinal implants for visual restoration; however, the visual acuity is still worse than legal blindness, and they require complex implant surgery. The present study aims to preclinically develop a photothermal stimulation approach with a less invasive process to restore visual response in blind mice.
Methods :
We intravitreally injected Thy-1 antibody-conjugated gold nanorods (Thy-1-AuNRs) in mice, specifically targeting retinal ganglion cells (RGCs) and then stimulated RGCs with near-infrared (NIR) laser, based on the well-studied phenomena of surface plasmon resonance and its photothermal effect. To validate the efficacy of this approach ex vivo, we combined a NIR laser scanning system and wide-filed fluorescence Ca2+ imaging microscope to evoke and record the neural activity of multiple RGCs on live retinal explants of GCaMP3 mice. For in vivo, we recorded electrocorticogram (ECoG) signals from the visual cortex of blind mice with Thy-1-AuNRs or PBS injection as illuminating the NIR laser on the retina.
Results :
Compared to PBS-injected retinas, the retinas with Thy-1-AuNRs of 980-nm resonance wavelength elicited highly localized Ca2+ responses of RGCs up to 5 % △F/F to a pattern of NIR laser pulses (980-nm wavelength, 0.1-ms pulses, 8-fps, 100 x 100 μm square-pattern) in a laser intensity-dependent manner. For in vivo, visual cortical neurons of the blind mice injected with Thy-1-AuNRs of 780-nm resonance wavelength were activated by NIR laser (780-nm, single 100-ms pulse, 50 trials averaged), producing evoked potentials of 44.4±8.8 µV (n=9), but PBS-injected mice did not respond to NIR light. The amplitude of the NIR-evoked potentials was similar to visually evoked potentials in wild-type mice (49.4±14.2µV, n=9; p=0.12).
Conclusions :
These findings suggest the promising potential of the minimally-invasive photothermal approach to restoring vision in blindness by remotely activating retinal neurons.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.