RNASeq profiling of retinal pigment epithelial cells derived from induced pluripotent stem cells revealed 3 genes involved in lipid homeostasis in age-related macular degeneration

Exp Eye Res. 2024 Sep:246:109999. doi: 10.1016/j.exer.2024.109999. Epub 2024 Jul 10.

Abstract

Age-related macular degeneration (AMD) is characterized by visual impairment observed in elderly population. Two forms of the disease are generally described, the atrophic (AMDa) and exudative forms (AMDe). Up until now, no curative treatment is available for this disease. The retinal pigment epithelium (RPE) plays a central role in the pathogenesis of age-related macular degeneration. Here, involvement of RPE dysfunction in AMD onset and progression was analyzed by a comparison of transcriptome profiles of hiPSC-RPE derived from healthy individuals or individuals affected by AMDa or AMDe. The analysis highlighted almost 1000 genes differentially expressed between the three comparison groups. Among these genes, 33 genes were already known to be involved in AMD pathogenesis. To establish an AMD genetic signature, we focused on genes differentially expressed in both AMDa/e cell lines compared to control cells and focused on the three genes (ABCA1, RPN2, RB1CC1) that were related to lipidic homeostasis. Differences in level expression of these three genes are found not only in control and AMDa/e cell lines, but also between AMDa and AMDe populations.

Keywords: Cell signaling; Cholesterol; Genomics; Lipids; Retina.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Cell Line
  • Homeostasis* / genetics
  • Humans
  • Induced Pluripotent Stem Cells* / cytology
  • Induced Pluripotent Stem Cells* / metabolism
  • Lipid Metabolism* / genetics
  • Macular Degeneration* / genetics
  • Macular Degeneration* / metabolism
  • Macular Degeneration* / pathology
  • Middle Aged
  • RNA-Seq
  • Retinal Pigment Epithelium* / cytology
  • Retinal Pigment Epithelium* / metabolism