Abstract
Purpose :
Vision restoration is possible in patients diagnosed with retinal degenerative diseases by artificially stimulating neuronal cell layers within the retina as long as they remain intact. By utilizing the unique localized surface plasmon resonance property of gold nanorods (AuNRs) and by conjugating them with an RGC-specific antibody (Thy 1.2), we can generate local heat by irradiating the AuNRs at their specific plasmon resonance band to stimulate the temperature-sensitive ion channels located on the membranes of RGCs. But it is unclear whether AuNRs can be successfully delivered to the retina via intravitreal injection and how long they remain within the retina when successful.
Methods :
We intravitreally (IVT) injected Thy1-AuNRs into the eyes of WT mice and euthanized them on different days post injection (DPI). To determine if glycosidic enzymes would facilitate the delivery of AuNRs to the retina, we co-injected a solution of AuNRs with glycosidic enzymes in another group. We used two-photon luminescence (TPL) imaging to detect AuNRs from live retinal explants. To determine the retinal layers AuNRs are most attached to, we utilized information acquired by separate DAPI imaging. In support of this, we additionally conducted simultaneous confocal imaging of DAPI and fluorescent AuNR-injected retinas. Finally, to quantify how long AuNRs remain within the retina, we dissected retinas for TPL imaging at 2, 8, 31, and 134 DPIs.
Results :
AuNR-injected retinas showed approximately 200x higher TPL intensities on average than the sham group (p<0.05). The mean TPL intensity decreased at 134 DPI, estimating a half-life time of 98 days (95% CI, 80-126 days). A comparison with DAPI images, in both the TPL and fluorescence experiments, indicated that most AuNRs were detected from the ganglion cell layer. The enzyme co-injected retinas did not exhibit higher TPL intensities.
Conclusions :
Intravitreally injected AuNRs were able to diffuse to RGCs via vitreous humor and remained there for several months. The co-injection of enzymes did not enhance AuNR delivery to the retina, suggesting that our AuNRs (25 nm diameter) can migrate and diffuse to the retina through the inner limiting membrane.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.