An Overview of Age-Related Macular Degeneration: Clinical, Pre-Clinical Animal Models and Bidirectional Translation

Age-related macular degeneration (AMD) is a multifactorial disease that results from a complex and unknown interplay among environmental, genetic, and epidemiologic factors. Risk factors include aging, family history, obesity, hypercholesterolemia, and hypertension, along with cigarette smoking, which is the most influential modifiable risk factor. Single nucleotide polymorphisms (SNPs) in numerous genes such as complement factor H (CFH) pose some of the known genetic risks. The pathophysiology in AMD is incompletely understood, but is known to involve oxidative stress, inflammation, dysregulated antioxidants, lipid metabolism, and angiogenesis. Animal models have been integral in expanding our knowledge of AMD pathology. AMD is classified as non-exudative or exudative. Because there is no perfect animal model that recapitulates all aspects of the human disease, rodents, rabbits, and non-human primates offer different advantages and disadvantages to serve as models for various aspects of the disease. Scientific advances have also allowed for the creation of polygenic pre-clinical models that may better represent the complexity of AMD, which will likely expand our knowledge of disease mechanisms and serve as platforms for testing new therapeutics. There have been, and there continues to be, many drugs in the pipeline to treat both exudative and non-exudative AMD. However, Food and Drug Administration (FDA)-approved therapies for exudative AMD that mainly target angiogenic growth factors are the only therapeutics currently being used in the clinics. There remains no FDA-approved therapy for the non-exudative form of this disease. This chapter contains a basic overview and classification of AMD and multiple animal models of AMD are highlighted. We include an overview of both current FDA-approved treatments and those in development. Lastly, we conclude with a summary of the important role of pre-clinical studies in the development of therapeutics for this highly prevalent disease.