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8 February 2017Longitudinal visualization of vascular occlusion, reperfusion, and remodeling in a zebrafish model of retinal vascular leakage using OCT angiography
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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Kathleen Spitz, Ivan Bozic, Vineet Desai, Gopikrishna M. Rao, Lana M. Pollock, Bela Anand-Apte, Yuankai K. Tao, "Longitudinal visualization of vascular occlusion, reperfusion, and remodeling in a zebrafish model of retinal vascular leakage using OCT angiography," Proc. SPIE 10045, Ophthalmic Technologies XXVII, 1004525 (8 February 2017); https://doi.org/10.1117/12.2252418