The global estimate of AMD cases was 196 million in 2020 and is expected to be 288 million by 2040. The disease burden will increase as the population ages with longer life expectancies. AMD is responsible for about 8.7% of blindness and remains as a leading cause of blindness in people over 60 years of age in the developed world. Non-exudative AMD is defined by the presence of drusen - aggregates of lipid, protein, and immune complexes - underneath the RPE with subsequent thickening of Bruch’s membrane. AMD is classified as non-exudative or exudative. AMD is a multifactorial disease of the elderly that progressively affects vision through pathological changes to the retinal pigment epithelium (RPE) and loss of photoreceptors in the macula. The macula, located in the posterior pole of the retina, contains the highest concentration of cone photoreceptors across the retina and is responsible for central, high-resolution, and color vision. The retina plays an integral role in vision by converting light to an electrical stimulus, which is ultimately processed as an image in the occipital lobe of the visual cortex. Lastly, we conclude with a summary of the important role of pre-clinical studies in the development of therapeutics for this highly prevalent disease. We include an overview of both current FDA-approved treatments and those in development. This chapter contains a basic overview and classification of AMD and multiple animal models of AMD are highlighted. There remains no FDA-approved therapy for the non-exudative form of this disease. 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 have been, and there continues to be, many drugs in the pipeline to treat both exudative and non-exudative AMD. 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. 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. Animal models have been integral in expanding our knowledge of AMD pathology. The pathophysiology in AMD is incompletely understood, but is known to involve oxidative stress, inflammation, dysregulated antioxidants, lipid metabolism, and angiogenesis. Single nucleotide polymorphisms (SNPs) in numerous genes such as complement factor H (CFH) pose some of the known genetic risks. Risk factors include aging, family history, obesity, hypercholesterolemia, and hypertension, along with cigarette smoking, which is the most influential modifiable risk factor. Age-related macular degeneration (AMD) is a multifactorial disease that results from a complex and unknown interplay among environmental, genetic, and epidemiologic factors.
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