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

Autor: Genichiro Kishino, Tetsuro Oshika, Simone Beheregaray, Toshiharu Yamashita, Masumi Nagano, Masahiro Fukuda, Osamu Ohneda, Hideko Nagasawa, Sujin Hoshi, Itsuki Kawano, Kensuke Okuda, Shinichi Fukuda
Rok vydání: 2015
Předmět:
Pathology
medicine.medical_specialty
genetic structures
Fundus Oculi
Fundus (eye)
Biology
010402 general chemistry
01 natural sciences
03 medical and health sciences
Cellular and Molecular Neuroscience
chemistry.chemical_compound
Mice
0302 clinical medicine
Retinal Diseases
In vivo
medicine
Electroretinography
Animals
Humans
Fluorescein Angiography
Hypoxia
Cells
Cultured

Fluorescent Dyes
Retinal Vascular Occlusion
Retina
Spectroscopy
Near-Infrared

medicine.diagnostic_test
Choroid
Reproducibility of Results
Retinal
Retinopathy of prematurity
medicine.disease
Fluorescein angiography
eye diseases
Sensory Systems
0104 chemical sciences
Mice
Inbred C57BL

Ophthalmology
Disease Models
Animal

medicine.anatomical_structure
Spectrometry
Fluorescence

chemistry
030221 ophthalmology & optometry
sense organs
Endothelium
Vascular

Rabbits
Preclinical imaging
Zdroj: Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie. 254(12)
ISSN: 1435-702X
Popis: 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. 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. 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. GPU-327 identified hypoxic area both in vivo and in vitro.
Databáze: OpenAIRE