Delivery and safety of gold nanorods for photothermal restoration of vision in blindness

Abstract

Electrical retinal prosthetics have been the primary strategy for restoring vision in individuals with blindness, relying on electrical stimulation from implanted electrodes. In this work, we explore the use of gold nanorods (AuNRs) as next-generation photothermal retinal prosthetics, enabling remote, light-driven activation of surviving retinal neurons. This study evaluates the influence of AuNR characteristics, size, conjugation, and concentration, on retinal delivery efficiency and both systemic and local toxicity following intravitreal injection. We tested three AuNR formulations: 25-nm Thy-conjugated AuNRs, 10-nm Thy-conjugated AuNRs, and 25 diameter bare AuNRs. Two concentrations (5 nM and 15 nM) were tested for the 25-nm diameter Thy- AuNRs. Using a mouse model, we assessed systemic toxicity through complete blood counts and serum biochemistry at multiple time points up to 128 days pots-injection. We also performed two-photon luminescence imaging of retinal flat mounts to quantify AuNR accumulation and asses intraretinal distribution. Our findings show that conjugation and size are key determinants of retinal accumulation, with Thy-conjugated 25-nm AuNRs displaying the highest retinal localization. Concentration-dependent effects were observed on circulating monocyte levels, while conjugation mildly influenced uric acid levels. Other toxicity markers remained within normal limits, and we found no evidence of retinal apoptosis at 128 days post-injection. Sex-related differences in hematological and serum biochemical parameters were consistent with published norms, but did not modify the toxicity profile of AuNRs. These results support the biocompatibility of Thy-conjugated 25-nm AuNRs and demonstrate their sustained presence in the retina following IVT delivery. Our findings underscore the importance of conjugation for both targeted and reduced systemic distribution. This work establishes foundational delivery and safety data to support the development of a minimally invasive, light-activated plasmonic retinal prosthesis.