Drusenoid Lesions in Membrane Metalloendopeptidase Mutant Mice as a Model of Age-Related Macular Degeneration

Abstract

Purpose : Age-related macular degeneration (AMD) is a leading cause of vision loss in the elderly, but there are few animal models of drusen as seen in non-exudative AMD. In this study, we evaluate drusenoid lesions in matrix metalloendopeptidase (MME) gene knock-out mice as a potential model of AMD.

Methods : C57BL/6 mice with MME (-/-) gene knock-out and drusen-like lesions were identified during phenotypic screening as part of the Mouse Biology Program at UC Davis. Full ophthalmic examination, fundus photography, fluorescein angiography (FA), optical coherence tomography (OCT) imaging, and electroretinographic (ERG) testing were performed.

Results : MME -/- mice had pale yellow circular lesions on fundus examination, which appeared hyperfluorescent on FA. On OCT, these dome-shaped lesions appear to be located underneath the retinal pigment epithelium (RPE) with associated disruption of overlying retinal layers, similar in appearance to soft drusen in human AMD. Full-field electroretinography shows overall normal retinal function in eyes with these lesions.

Conclusions : Retinal lesions in the MME -/- mutant mice may resemble soft drusen in eyes with AMD. Further characterization of this mutant mouse model may provide insight into drusen biogenesis and the pathogenesis of AMD.

This is a 2020 ARVO Annual Meeting abstract.