Longitudinal Progression of Laser Induced Choroidal Neovascularization in Mice-Effect of age and sex

Abstract

Purpose : Wet age-related macular degeneration (wAMD) is the leading cause of vision loss in the elderly population. wAMD is characterized by abnormal proliferation and invasion of the choroidal vasculature into the sub-RPE and subretinal spaces, which is often accompanied by leakage of plasma. The specific biological factors that predispose to CNV and its progression are currently unknown. Longitudinal in-vivo imaging was used to examine the long-term effects of age and sex on CNV progression and healing in mice.

Methods : Laser-induced CNV was generated in male and female young (2-month-old) and aged (12-month old) C57BL6 mice by making 3 separate sub retinal burns in each eye with a diode laser. Fluorescein angiography and OCT imaging was performed at days 3, 7, 10, 14, 21 and 28-post injury. Early phase images of fluorescein angiography (FA) and ICG were taken at ~3 mins and late phase images were taken at ~6 mins. Ultra high-resolution spectral domain optical coherence tomography (OCT) system was used for in-vivo cross-sectional imaging. Lesion volume was measured from volumetric OCT images. SLO images were analyzed in Image J (Version 1.52a) for lesion size and leakage. The CNV volume was measured using the InVivoVue software (v2.4 Bioptigen Inc.).

Results : While the initial lesion size and leakage was the same in young and old mice, resolution of the “leakiness” and size was slower in older mice. Young mice showed a more rapid recovery over time compared to old mice (Fig.1a-b). The early and late phase FA exhibit arterial and venous phase of blood flow, respectively. The FA data shows a statistically significant decrease in leakage area over time in both groups, however the rate and extent of healing was faster in young mice compared with old mice. The OCT based lesion volume measurement exhibits structural assessment of CNV progression over time (Fig.2). The OCT data shows a statistically significant (up to day-14 time point) decrease in lesion volume over time in both groups; however the rate and extent of healing was faster in young mice (2 month) compared with old mice (12 month).

Conclusions : Aged mice are more susceptible to laser-induced CNV formation and delayed healing. The lesion size (leakage area) in young mice showed rapid healing over time compared with old mice. Sex was not a significant contributor.

This is a 2021 Imaging in the Eye Conference abstract.