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Graefes Arch Clin Exp Ophthalmol. 2016 Dec;254(12):2373-2385. Epub 2016 Aug 29.

In vivo retinal and choroidal hypoxia imaging using a novel activatable hypoxia-selective near-infrared fluorescent probe.

Author information

1
Department of Ophthalmology, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.
2
Laboratory of Bioorganic & Natural Products Chemistry, Kobe Pharmaceutical University, Kobe, Japan.
3
Laboratory of Pharmaceutical and Medicinal Chemistry, Gifu Pharmaceutical University, Gifu, Japan.
4
Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan.
5
Laboratory of Regenerative Medicine and Stem Cell Biology, Graduate School of Comprehensive Human Science, University of Tsukuba, Ibaraki, Japan.
6
Department of Ophthalmology, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan. oshika@eye.ac.

Abstract

PURPOSE:

Retinal hypoxia plays a crucial role in ocular neovascular diseases, such as diabetic retinopathy, retinopathy of prematurity, and retinal vascular occlusion. Fluorescein angiography is useful for identifying the hypoxia extent by detecting non-perfusion areas or neovascularization, but its ability to detect early stages of hypoxia is limited. Recently, in vivo fluorescent probes for detecting hypoxia have been developed; however, these have not been extensively applied in ophthalmology. We evaluated whether a novel donor-excited photo-induced electron transfer (d-PeT) system based on an activatable hypoxia-selective near-infrared fluorescent (NIRF) probe (GPU-327) responds to both mild and severe hypoxia in various ocular ischemic diseases animal models.

METHODS:

The ocular fundus examination offers unique opportunities for direct observation of the retina through the transparent cornea and lens. After injection of GPU-327 in various ocular hypoxic diseases of mouse and rabbit models, NIRF imaging in the ocular fundus can be performed noninvasively and easily by using commercially available fundus cameras. To investigate the safety of GPU-327, electroretinograms were also recorded after GPU-327 and PBS injection.

RESULT:

Fluorescence of GPU-327 increased under mild hypoxic conditions in vitro. GPU-327 also yielded excellent signal-to-noise ratio without washing out in vivo experiments. By using near-infrared region, GPU-327 enables imaging of deeper ischemia, such as choroidal circulation. Additionally, from an electroretinogram, GPU-327 did not cause neurotoxicity.

CONCLUSIONS:

GPU-327 identified hypoxic area both in vivo and in vitro.

KEYWORDS:

Hypoxia imaging; In vivo imaging; Near-infrared fluorescent probe; Ocular ischemia

PMID:
27572140
DOI:
10.1007/s00417-016-3476-x
[Indexed for MEDLINE]

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