Angiographic features of transgenic mice with increased expression of human serine protease htra1 in retinal pigment epithelium

Sandeep Kumar, Zachary Berriochoa, Balamurali K. Ambati, Yingbin Fu

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3842-3850
Number of pages9
JournalInvestigative Ophthalmology and Visual Science
Volume55
Issue number6
DOIs
StatePublished - Jun 19 2014
Externally publishedYes

Keywords

  • HTRA1
  • Indocyanine green angiography
  • Late geographic hyperfluorescence
  • Pigment epithelial detachment
  • Polypoidal choroidal vasculopathy

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'Angiographic features of transgenic mice with increased expression of human serine protease htra1 in retinal pigment epithelium'. Together they form a unique fingerprint.

Cite this