We examined the efficacy of Indocyanine Green (ICG) loaded plasmonic gold nanorods (AuNP) assisted combined photothermal and photodynamic therapy for laser induced choroidal neovascularization (CNV) in pigmented mice. Eight C57BL/6 wild type pigmented mice were divided into two treatment groups. Each mouse received multiple 532 nm laser induced CNV in both eyes. Control mice were untreated while treatment group received intravenous injection of ICG loaded gold nanorods on day 7 prior to single near-infrared (NIR 808 nm) laser treatment session. For assessing progression of CNV lesion volume, in-vivo ocular imaging was performed on each animal at day 1, 7, and 14 using optical coherence tomography volumetric imaging. Early and late phase fluorescence angiography was performed for CNV leakage analysis. Infrared reflectance imaging and were used to analyze in-vivo laser injury and healing assessment. ICG-AuNP assisted combined photothermal/photodynamic therapy resulted in significantly increased healing and decreased fluorescein leakage at the CNV site compared to control mice who did not receive NIR laser treatment. Enhanced permeability and retention of AuNP assists in localization of therapeutic agents to the CNV lesion, which allows for targeted therapy while minimizing laser induced damage to healthy tissues.
Diabetic retinopathy (DR) and age-related macular degeneration (AMD) are two of the leading causes of blindness and
visual impairment in the world. Neovascularization results in severe vision loss in DR and AMD and, thus, there is an
unmet need to identify mechanisms of pathogenesis and novel anti-angiogenic therapies. Zebrafish is a leading model
organism for studying human disease pathogenesis, and the highly conserved drug activity between zebrafish and humans
and their ability to readily absorb small molecules dissolved in water has benefited pharmaceutical discovery. Here, we
use optical coherence tomography (OCT) and OCT angiography (OCT-A) to perform noninvasive, in vivo retinal imaging
in a zebrafish model of vascular leakage. Zebrafish were treated with diethylaminobenzaldehyde (DEAB) to induce
vascular leakage and imaged with OCT and OCT-A at six time points over two weeks: baseline one day before treatment
and one, three, six, eight, and ten days post treatment. Longitudinal functional imaging showed significant vascular
response immediately after DEAB treatment. Observed vascular changes included partial or complete vascular occlusion
immediately after treatment and reperfusion during a two-week period. Increased vascular tortuosity several days post
treatment indicated remodeling, and bifurcations and collateral vessel formation were also observed. In addition,
significant treatment response variabilities were observed in the contralateral eye of the same animal. Anatomical and
functional normalization was observed in most animals by ten days post treatment. These preliminary results motivate
potential applications of OCT-A as a tool for studying pathogenesis and therapeutic screening in zebrafish models of
retinal vascular disease.
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