Generation of Transplantable Retinal Pigmented Epithelial (RPE) Cells for Treatment of Age-Related Macular Degeneration (AMD)

Methods Mol Biol. 2019;2045:283-298. doi: 10.1007/7651_2018_140.

Abstract

Age-related macular degeneration (AMD) is the foremost cause of blindness in people over the age of 60 worldwide. Clinically, this disease starts with distortion in central vision eventually leading to legal blindness. Vision loss has a significant impact on quality of life and incurs a substantial cost to the economy. Furthermore, AMD is a complex and progressive neurodegenerative disorder that triggers visual impairment due to the loss of retinal pigmented epithelium (RPE) and the light-sensitive photoreceptors that they support, protect and provide nutrition. Currently, there is no curative treatment for the most common form of this disease, i.e., dry AMD. A novel approach to treat AMD involves the transplantation of RPE cells derived from human induced pluripotent stem cells (iPSCs) in the outer retina. These iPSC-derived RPE cells not only show characteristics similar to native RPE but also could replace as well as regenerate damaged pathologic RPE and produce supportive growth factors and cytokines. Several clinical trials are being conducted taking advantage of a variety of cell- and tissue engineering-based approaches. Here, we present a simple, cost effective, and scalable cell-culture model for generation of purified RPE thus providing the foundation for developing an allogeneic cell therapy for AMD.

Keywords: Age-related macular degeneration; Eye; Induced pluripotent stem cells; Retina; Retinal pigment epithelial cells.

MeSH terms

  • ADP-Ribosylation Factors / metabolism
  • Antibodies / metabolism
  • Cell Culture Techniques / methods*
  • Cell Differentiation* / drug effects
  • Cells, Cultured
  • Collagen / chemistry
  • Drug Combinations
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Humans
  • Induced Pluripotent Stem Cells / cytology*
  • Induced Pluripotent Stem Cells / drug effects
  • Induced Pluripotent Stem Cells / metabolism
  • Laminin / chemistry
  • Macular Degeneration / therapy*
  • Nestin / metabolism
  • Octamer Transcription Factor-3 / metabolism
  • PAX6 Transcription Factor / metabolism
  • Polymerase Chain Reaction
  • Proteoglycans / chemistry
  • Retinal Pigment Epithelium / cytology*
  • Retinal Pigment Epithelium / metabolism
  • Retinal Pigment Epithelium / transplantation*
  • Transcription Factor Brn-3A / metabolism
  • Workflow
  • cis-trans-Isomerases / metabolism

Substances

  • Antibodies
  • Drug Combinations
  • Laminin
  • NES protein, human
  • Nestin
  • Octamer Transcription Factor-3
  • PAX6 Transcription Factor
  • POU4F1 protein, human
  • POU5F1 protein, human
  • Proteoglycans
  • Transcription Factor Brn-3A
  • matrigel
  • Collagen
  • retinoid isomerohydrolase
  • ADP-Ribosylation Factors
  • Arl13b protein, human
  • cis-trans-Isomerases