A Review of Pathogenic Drivers of Age-Related Macular Degeneration, Beyond Complement, with a Focus on Potential Endpoints for Testing Therapeutic Interventions in Preclinical Studies

Abstract

Age-related macular degeneration (AMD) continues to be the leading cause of visual impairment for the elderly in developed countries. It is a complex, multifactorial, progressive disease with diverse molecular pathways regulating its pathogenesis. One of the cardinal features of the early clinical subtype of AMD is the accumulation of lipid- and protein-rich deposits within Bruch's membrane, called drusen, which can be visualized by fundus imaging. Currently, multiple in vitro and in vivo model systems exist, which can be used to help tease out mechanisms associated with different molecular pathways driving disease initiation and progression. Given the lack of treatments for patients suffering from the dry form of AMD, it is imperative to appreciate the different known morphological endpoints associated with the various pathogenic pathways, in order to derive further insights, for the ultimate purpose of disease modeling and development of effective therapeutic interventions.

Keywords: Age-related macular degeneration; Apolipoprotein; Cholesterol; Inflammation; Lipid metabolism; Quick-freeze/deep etch; Retinal pigment epithelial cells.