Multi-Functional OCT Enables Longitudinal Study of Retinal Changes in a VLDLR Knockout Mouse Model

PLoS One. 2016 Oct 6;11(10):e0164419. doi: 10.1371/journal.pone.0164419. eCollection 2016.

Abstract

We present a multi-functional optical coherence tomography (OCT) imaging approach to study retinal changes in the very-low-density-lipoprotein-receptor (VLDLR) knockout mouse model with a threefold contrast. In the retinas of VLDLR knockout mice spontaneous retinal-chorodoidal neovascularizations form, having an appearance similar to choroidal and retinal neovascularizations (CNV and RNV) in neovascular age-related macular degeneration (AMD) or retinal angiomatous proliferation (RAP). For this longitudinal study, the mice were imaged every 4 to 6 weeks starting with an age of 4 weeks and following up to the age of 11 months. Significant retinal changes were identified by the multi-functional imaging approach offering a threefold contrast: reflectivity, polarization sensitivity (PS) and motion contrast based OCT angiography (OCTA). By use of this intrinsic contrast, the long-term development of neovascularizations was studied and associated processes, such as the migration of melanin pigments or retinal-choroidal anastomosis, were assessed in vivo. Furthermore, the in vivo imaging results were validated with histological sections at the endpoint of the experiment. Multi-functional OCT proves as a powerful tool for longitudinal retinal studies in preclinical research of ophthalmic diseases. Intrinsic contrast offered by the functional extensions of OCT might help to describe regulative processes in genetic animal models and potentially deepen the understanding of the pathogenesis of retinal diseases such as wet AMD.

MeSH terms

  • Animals
  • Choroidal Neovascularization / diagnostic imaging
  • Choroidal Neovascularization / pathology
  • Image Processing, Computer-Assisted
  • Longitudinal Studies
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, LDL / deficiency
  • Receptors, LDL / genetics*
  • Retina / diagnostic imaging*
  • Retina / pathology
  • Retina / physiology
  • Retinal Neovascularization / diagnostic imaging
  • Retinal Neovascularization / pathology
  • Tomography, Optical Coherence

Substances

  • Receptors, LDL
  • VLDL receptor

Grant support

This work was funded by the Austrian Science Fund (FWF grant P25823-B24 to BB; https://www.fwf.ac.at/) and the European Research Council (ERC StG 640396 OPTIMALZ to BB; https://erc.europa.eu/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.