PMID- 24854852
OWN - NLM
STAT- MEDLINE
DCOM- 20140903
LR  - 20231213
IS  - 1552-5783 (Electronic)
IS  - 0146-0404 (Print)
IS  - 0146-0404 (Linking)
VI  - 55
IP  - 6
DP  - 2014 May 22
TI  - Angiographic features of transgenic mice with increased expression of human 
      serine protease HTRA1 in retinal pigment epithelium.
PG  - 3842-50
LID - 10.1167/iovs.13-13111 [doi]
AB  - PURPOSE: Polypoidal choroidal vasculopathy (PCV) is characterized by a branching 
      vascular network (BVN) of choroid that terminates in polypoidal dilations. We 
      have previously reported the generation of the first PCV model by transgenically 
      expressing human HTRA1 (hHTRA1(+)), a multifunctional serine protease, in mouse 
      RPE. The purpose of this study was to perform a comprehensive examination of the 
      PCV phenotypes (e.g., lesion type and distribution) of hHTRA1(+) mice by a 
      variety of in vivo imaging techniques. METHODS: We generated improved hHTRA1(+) 
      mice with a more consistent phenotype. Transgenic mice were examined by 
      indocyanine green angiography (ICGA), fluorescein angiography, funduscopy, and 
      spectral-domain optical coherence tomography. In particular, we performed ICGA by 
      tail vein injection of ICG to obtain high-quality ICGA comparable to human 
      studies in terms of the three phases (early, middle, and late) of angiography. 
      RESULTS: The polyps can be detected in the early "fill-in" phase of ICGA, and 
      most lesions become visible in the middle phase and are more distinct in the late 
      phase with the fading of surrounding vessels. In addition to the two key features 
      of PCV (polypoidal dilations and BVNs), hHTRA1(+) mice exhibit other features of 
      PCV (i.e., late geographic hyperfluorescence, pigment epithelial detachment, and 
      hyperfluorescent plaque). Polypoidal lesions appear as reddish orange nodules on 
      funduscopy. CONCLUSIONS: Transgenic hHTRA1(+) mice exhibit a rich spectrum of 
      "clinical" features that closely mimic human PCV. This animal model will serve as 
      an invaluable tool for future mechanistic and translational studies of PCV and 
      other forms of choroidal vasculopathies.
CI  - Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.
FAU - Kumar, Sandeep
AU  - Kumar S
AD  - Department of Ophthalmology and Visual Sciences, University of Utah Health 
      Sciences Center, Salt Lake City, Utah, United States.
FAU - Berriochoa, Zachary
AU  - Berriochoa Z
AD  - Department of Ophthalmology and Visual Sciences, University of Utah Health 
      Sciences Center, Salt Lake City, Utah, United States.
FAU - Ambati, Balamurali K
AU  - Ambati BK
AD  - Department of Ophthalmology and Visual Sciences, University of Utah Health 
      Sciences Center, Salt Lake City, Utah, United States Department of Neurobiology 
      and Anatomy, University of Utah Health Sciences Center, Salt Lake City, Utah, 
      United States.
FAU - Fu, Yingbin
AU  - Fu Y
AD  - Department of Ophthalmology and Visual Sciences, University of Utah Health 
      Sciences Center, Salt Lake City, Utah, United States Department of Neurobiology 
      and Anatomy, University of Utah Health Sciences Center, Salt Lake City, Utah, 
      United States.
LA  - eng
GR  - P30 EY014800/EY/NEI NIH HHS/United States
GR  - R01 EY022901/EY/NEI NIH HHS/United States
GR  - 5P30EY014800/EY/NEI NIH HHS/United States
GR  - 1R01EY022901/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20140522
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 0 (Coloring Agents)
RN  - EC 3.4.21.- (High-Temperature Requirement A Serine Peptidase 1)
RN  - EC 3.4.21.- (HTRA1 protein, human)
RN  - EC 3.4.21.- (Serine Endopeptidases)
RN  - IX6J1063HV (Indocyanine Green)
SB  - IM
MH  - Aged
MH  - Animals
MH  - Blotting, Western
MH  - Choroidal Neovascularization/genetics/*pathology
MH  - Coloring Agents
MH  - *Disease Models, Animal
MH  - Female
MH  - *Fluorescein Angiography
MH  - Gene Expression Regulation/*physiology
MH  - High-Temperature Requirement A Serine Peptidase 1
MH  - Humans
MH  - Immunohistochemistry
MH  - Indocyanine Green
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Middle Aged
MH  - Phenotype
MH  - Polyps/genetics/*pathology
MH  - Retinal Pigment Epithelium/*metabolism/pathology
MH  - Serine Endopeptidases/*genetics
MH  - Tomography, Optical Coherence
PMC - PMC4581615
OTO - NOTNLM
OT  - HTRA1
OT  - indocyanine green angiography
OT  - late geographic hyperfluorescence
OT  - pigment epithelial detachment
OT  - polypoidal choroidal vasculopathy
EDAT- 2014/05/24 06:00
MHDA- 2014/09/04 06:00
PMCR- 2014/12/01
CRDT- 2014/05/24 06:00
PHST- 2014/05/24 06:00 [entrez]
PHST- 2014/05/24 06:00 [pubmed]
PHST- 2014/09/04 06:00 [medline]
PHST- 2014/12/01 00:00 [pmc-release]
AID - iovs.13-13111 [pii]
AID - 10.1167/iovs.13-13111 [doi]
PST - epublish
SO  - Invest Ophthalmol Vis Sci. 2014 May 22;55(6):3842-50. doi: 10.1167/iovs.13-13111.