PMID- 28750413
OWN - NLM
STAT- MEDLINE
DCOM- 20170811
LR  - 20200415
IS  - 1552-5783 (Electronic)
IS  - 0146-0404 (Print)
IS  - 0146-0404 (Linking)
VI  - 58
IP  - 9
DP  - 2017 Jul 1
TI  - In Vivo Imaging of Retinal Hypoxia Using HYPOX-4-Dependent Fluorescence in a 
      Mouse Model of Laser-Induced Retinal Vein Occlusion (RVO).
PG  - 3818-3824
LID - 10.1167/iovs.16-21187 [doi]
AB  - PURPOSE: To demonstrate the utility of a novel in vivo molecular imaging probe, 
      HYPOX-4, to detect and image retinal hypoxia in real time, in a mouse model of 
      retinal vein occlusion (RVO). METHODS: Retinal vein occlusion was achieved in 
      adult mice by photodynamic retinal vein thrombosis (PRVT). One or two major 
      retinal vein(s) was/were occluded in close proximity to the optic nerve head 
      (ONH). In vivo imaging of retinal hypoxia was performed using, HYPOX-4, an 
      imaging probe developed by our laboratory. Pimonidazole-adduct immunostaining was 
      performed and used as a standard ex vivo method for the detection of retinal 
      hypoxia in this mouse RVO model. The retinal vasculature was imaged using 
      fluorescein angiography (FA) and isolectin B4 staining. Retinal thickness was 
      assessed by spectral-domain optical coherence tomography (SD-OCT) analysis. 
      RESULTS: By application of the standard ex vivo pimonidazole-adduct 
      immunostaining technique, retinal hypoxia was observed within 2 hours post-PRVT. 
      The observed hypoxic retinal areas depended on whether one or two retinal vein(s) 
      was/were occluded. Similar areas of hypoxia were imaged in vivo using HYPOX-4. 
      Using OCT, retinal edema was observed immediately post-PRVT induction, resolving 
      8 days later. Nominal preretinal neovascularization was observed at 10 to 14 days 
      post-RVO. CONCLUSIONS: HYPOX-4 is an efficient probe capable of imaging retinal 
      hypoxia in vivo, in RVO mice. Future studies will focus on its use in correlating 
      retinal hypoxia to the onset and progression of ischemic vasculopathies.
FAU - Uddin, Md Imam
AU  - Uddin MI
AD  - Department of Ophthalmology and Visual Sciences, Vanderbilt University School of 
      Medicine, Nashville, Tennessee, United States.
FAU - Jayagopal, Ashwath
AU  - Jayagopal A
AD  - Pharma Research and Early Development, Roche Innovation Center Basel, F. 
      Hoffmann-La Roche, Ltd. Basel, Switzerland.
FAU - McCollum, Gary W
AU  - McCollum GW
AD  - Department of Ophthalmology and Visual Sciences, Vanderbilt University School of 
      Medicine, Nashville, Tennessee, United States.
FAU - Yang, Rong
AU  - Yang R
AD  - Department of Ophthalmology and Visual Sciences, Vanderbilt University School of 
      Medicine, Nashville, Tennessee, United States.
FAU - Penn, John S
AU  - Penn JS
AD  - Department of Ophthalmology and Visual Sciences, Vanderbilt University School of 
      Medicine, Nashville, Tennessee, United States 2Pharma Research and Early 
      Development, Roche Innovation Center Basel, F. Hoffmann-La Roche, Ltd. Basel, 
      Switzerland 3Department of Molecular Physiology and Biophysics, Vanderbilt 
      University School of Medicine, Nashville, Tennessee, United States 4Department of 
      Cell and Developmental Biology, Vanderbilt University School of Medicine, 
      Nashville, Tennessee, United States.
LA  - eng
GR  - S10 OD021630/OD/NIH HHS/United States
GR  - U24 DK076169/DK/NIDDK NIH HHS/United States
GR  - P30 EY008126/EY/NEI NIH HHS/United States
GR  - P30 DK020593/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 0 (Fluoresceins)
RN  - 0 (Fluorescent Dyes)
RN  - 0 (HYPOX-4 compound)
RN  - 0 (Nitroimidazoles)
RN  - 0 (Radiation-Sensitizing Agents)
RN  - 46JO4D76R2 (pimonidazole)
SB  - IM
MH  - Animals
MH  - *Disease Models, Animal
MH  - Fluorescein Angiography
MH  - Fluoresceins/*administration & dosage/chemical synthesis
MH  - Fluorescent Dyes/*administration & dosage/chemical synthesis
MH  - Hypoxia/*diagnostic imaging
MH  - Image Processing, Computer-Assisted
MH  - Macular Edema/diagnosis
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Nitroimidazoles/*administration & dosage/chemical synthesis
MH  - Radiation-Sensitizing Agents/administration & dosage
MH  - Retinal Neovascularization/diagnosis
MH  - Retinal Vein/*diagnostic imaging
MH  - Retinal Vein Occlusion/*diagnostic imaging
MH  - Tomography, Optical Coherence
PMC - PMC5531786
EDAT- 2017/07/28 06:00
MHDA- 2017/08/12 06:00
PMCR- 2017/07/01
CRDT- 2017/07/28 06:00
PHST- 2017/07/28 06:00 [entrez]
PHST- 2017/07/28 06:00 [pubmed]
PHST- 2017/08/12 06:00 [medline]
PHST- 2017/07/01 00:00 [pmc-release]
AID - 2646756 [pii]
AID - IOVS-16-21187 [pii]
AID - 10.1167/iovs.16-21187 [doi]
PST - ppublish
SO  - Invest Ophthalmol Vis Sci. 2017 Jul 1;58(9):3818-3824. doi: 
      10.1167/iovs.16-21187.