Models of Pathologies Associated with Age-Related Macular Degeneration and Their Utilities in Drug Discovery
Age-related macular degeneration is the leading cause of vision loss in the elderly in the developed world, with an ever-increasing prevalence in the developing world. The complexity of the disease and lack of effective therapies speak to the necessity of
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Models of Pathologies Associated with Age-Related Macular Degeneration and Their Utilities in Drug Discovery Goldis Malek, Pei-Li Yao, and Mayur Choudhary
Contents 1 Introduction 2 AMD-Relevant In Vitro Cell Modeling 2.1 Primary Culture Cells 2.2 Continuous Cell Lines 2.3 hESC- or iPSC-Derived Cells 2.4 Disease-Relevant Mechanistic Endpoints Using In Vitro Cell Models 3 In Vivo Models of AMD 3.1 Mouse Models of Dry AMD 3.2 Mouse Models of Wet Macular Degeneration 3.3 Nonhuman Primate Models of AMD 4 Conclusions References
Abstract Age-related macular degeneration is the leading cause of vision loss in the elderly in the developed world, with an ever-increasing prevalence in the developing world. The complexity of the disease and lack of effective therapies speak to the necessity of further understanding the pathobiology and mechanisms underlying initiation and progression of this retinal neurodegenerative disease, as well as identifying new therapeutic targets. Designing and characterizing cell culture and animal models that promulgate the human AMD condition provide preclinical avenues to address these two unmet needs. Herein we discuss strengths and weaknesses associated with current in vitro and in vivo models available that facilitate testing of potential AMD-targeting drugs and discovery of new pathways involved in disease development.
G. Malek (*) Departments of Ophthalmology and Pathology, Albert Eye Research Institute, Duke University, Durham, NC, USA e-mail: [email protected] P.-L. Yao and M. Choudhary Department of Ophthalmology, Duke University, Durham, NC, USA e-mail: [email protected]; [email protected]
G. Malek et al.
Keywords Age-related macular degeneration (AMD), Animal models, Choroidal endothelial cells (ChEC), Choroidal neovascularization (CNV), Lipid metabolism, Oxidative stress, Retinal organoids, Retinal pigment epithelium (RPE), Sub-RPE deposits
Abbreviations A2E ABCA1 AhR AMD APOE BrM CDH5 CEP CETP CFH ChEC CNV CRALBP CSE CX3CR1 DHA ECM EGFR EMT ERK ESC-RPE FAK FBS GWAS H2O2 HDL HFD hfRPE HMGCS2 HPV INSIG1 iPSC-RPE KEAP1 LDL LIPC NRF2 OCT
Diretinoid-pyridinium-ethanolamine ATP-binding cassette transporter A1 Aryl hydrocarbon receptor Age-related macular degeneration Apolipoprotein E Bruch’s membrane Cadherin 5 Carboxyethylpyrrole Cholesterol ester transfer protein Complement factor H Choroidal endothelial cells Choroidal neovascularization Cellular retinaldehyde-binding protein Cigarette smoke extract C-X3-C motif chemokine receptor 1 Docosahexaenoic acid Extracellular matrix Epidermal growth factor receptor Epithelial-mesenchymal transition Extracellular signal-regulated kinases Embryonic stem cell-derived RPE cells Focal adhesion kinase Fetal bovine serum Genome-wide association study Hydrogen peroxide High-density lipoprotein High-fat diet Human fetal RPE cells 3-Hydroxy-3-methylglutaryl-coA synthase 2 Human papilloma virus Insulin-induced gene-1 Induced pluripotent stem cell-derived RPE Kelch-like ECH-associated protein 1 Low-density lipoproteins Hepatic lipase Nuclear fact
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