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Models of Pathologies Associated with Age-Related Macular Degeneration and Their Utilities in Drug Discovery

  • Goldis MalekEmail author
  • Pei-Li Yao
  • Mayur Choudhary
Part of the Topics in Medicinal Chemistry book series


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.


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 





ATP-binding cassette transporter A1


Aryl hydrocarbon receptor


Age-related macular degeneration


Apolipoprotein E


Bruch’s membrane


Cadherin 5




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 factor 2


Optical coherence tomography


Octamer-binding transcription factor ¾


Paired box 6


Platelet and endothelial cell adhesion molecule 1


Plasmalemma vesicle-associated protein


Proliferator-activated receptor beta/delta




All-trans-retinol dehydrogenases


Reactive oxygen species


Retinal pigment epithelium


Retinal pigment epithelial stem cells


Superoxide dismutase


Src proto-oncogene, non-receptor tyrosine kinase


Spleen associated tyrosine kinase


TGFβ type I receptor


Transforming growth factor beta


Translocator protein


Vascular endothelial growth factor A


Very low-density lipoprotein receptor


Zonula occludens 1



We thank our funding agencies [National Eye Institute grants R01 EY027802 and R01 EY028160 (to GM), P30 EY005722 (to the Duke Eye Center), and the Research to Prevent Blindness, Inc. (RPB) Core grant (to the Duke Eye Center)] for their continued support of our ongoing research and quest to understand complex retinal diseases and identify new therapeutic targets. We also express our gratitude to the donors and their families for their generosity.

Compliance with Ethical Standards

Funding: This study was funded by National Eye Institutes grants R01 EY028702 and R01 EY028160 (to GM), P30 EY005722 (to the Duke Eye Center), and the Research to Prevent Blindness, Inc. (RPB) Core grant (to the Duke Eye Center).

Ethical Approval: Donor tissues obtained are used following approval from the Duke Institutional Review Board (IRB) committee. Similarly, animal studies are performed following protocol approval from the Duke Institutional Animal Care and Use Committee (IACUC).

Informed Consent: Not applicable.

Conflict of Interest: The authors have no conflicts of interest to disclose.


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© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Departments of Ophthalmology and Pathology, Albert Eye Research InstituteDuke UniversityDurhamUSA
  2. 2.Department of OphthalmologyDuke UniversityDurhamUSA

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