Abstract
To investigate the early development of spontaneous retinal neovascularization in the murine retina by a multifunctional optical coherence tomography approach. To characterize involved tissue changes in vivo and describe structural and functional changes over time. A multifunctional optical coherence tomography (OCT) system providing 3-fold contrast comprising reflectivity, polarization sensitivity, and OCT angiography (OCTA) was utilized to image very-low-density lipoprotein receptor (VLDLR) knockout mice. Baseline measurements were acquired as early as postnatal day 14 and a follow-up of neovascularization development was performed until the age of 3 months. Control mice were imaged accordingly and a multiparametric image analysis was performed to characterize different stages of pathologic vascular growth. Histology was conducted at the endpoint of the experiment. An interventional pilot experiment was conducted to investigate the effect of the anti-vascular endothelial growth factor (VEGF) agent aflibercept on the development of retinal neovascularization. Onset of neovascularization was imaged at baseline, and significant changes were encountered in the retina over time, including reduced retinal thickness, increase of lesion volume, migration of pigmented structures, and presence of abnormal blood flow in the outer retina. Multifunctional image contrast was correlated to ex vivo histology. Microscopic analysis of retinal flat mounts and cross-sectional samples confirmed the changes observed in in vivo structural and functional OCT images. Administration of an anti-VEGF agent resulted in a significantly reduced lesion volume. Longitudinal, multifunctional OCT imaging of infant VLDLR-/- mouse retinas enabled a multiparametric, in vivo staging of neovascularization formation from before lesion onset until their manifestation.
Highlights
In Vivo Characterization of Spontaneous Retinal Neovascularization in the Mouse Eye by Multifunctional Optical Coherence Tomography
An interventional pilot experiment was conducted to investigate the effect of the anti-vascular endothelial growth factor (VEGF) agent aflibercept on the development of retinal neovascularization
While type 1 vascular lesions originate beneath the retinal pigment epithelium (RPE), type 2 neovascularizations are associated with the growth of new vessels in the subsensory retina.[2]
Summary
A multifunctional optical coherence tomography (OCT) system providing 3-fold contrast comprising reflectivity, polarization sensitivity, and OCT angiography (OCTA) was utilized to image very-low-density lipoprotein receptor (VLDLR) knockout mice. All mice in the KO and CO groups were initially imaged at P17 (62.0), which served as a baseline (BL) measurement. Mice in the IKO group were imaged at P14 (60.0), P28, P57, P85, and P122 (all 60.5). Mice were antagonized with 0.2 mg/kg atipamezole (Antisedan; Orion Corporation, Espoo, Finnland) s.c. if necessary after 1 hour. Both eyes of the KO and CO groups were imaged at every time point. Both eyes of IKO mice were imaged at F1 through F4 while only the interventional eye was imaged at the BL to reduce the time under anesthesia required for the experiment
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