Angiographic features of transgenic mice with increased expression of human serine protease HTRA1 in retinal pigment epithelium.
OBJECTIVE
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.
Department of Ophthalmology and Visual Sciences, University of Utah Health Sciences Center, Salt Lake City, Utah, United States.
Sandeep
S
Kumar
Department of Ophthalmology and Visual Sciences, University of Utah Health Sciences Center, Salt Lake City, Utah, United States.
Zachary
Z
Berriochoa
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.
Balamurali K
BK
Ambati
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.
Yingbin
Y
Fu
D000368:Aged; D000818:Animals; D015153:Blotting, Western; D020256:Choroidal Neovascularization / Q000235:genetics / Q000473:pathology*; D004396:Coloring Agents; D004195:Disease Models, Animal; D005260:Female; D005451:Fluorescein Angiography; D005786:Gene Expression Regulation / Q000502:physiology*; D000074289:High-Temperature Requirement A Serine Peptidase 1; D006801:Humans; D007150:Immunohistochemistry; D007208:Indocyanine Green; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008875:Middle Aged; D010641:Phenotype; D011127:Polyps / Q000235:genetics / Q000473:pathology*; D055213:Retinal Pigment Epithelium / Q000378:metabolism* / Q000473:pathology; D012697:Serine Endopeptidases / Q000235:genetics*; D041623:Tomography, Optical Coherence
D004396:Coloring Agents; D000074289:High-Temperature Requirement A Serine Peptidase 1; C474012:HTRA1 protein, human; D012697:Serine Endopeptidases; D007208:Indocyanine Green
HTRA1; indocyanine green angiography; late geographic hyperfluorescence; pigment epithelial detachment; polypoidal choroidal vasculopathy