2. Academic Validation
  3. The effects of pigment epithelium-derived factor and associated peptides on the differentiation of retinal ganglion cells from human-induced pluripotent stem cells

The effects of pigment epithelium-derived factor and associated peptides on the differentiation of retinal ganglion cells from human-induced pluripotent stem cells

  • Exp Eye Res. 2025 Aug:257:110440. doi: 10.1016/j.exer.2025.110440.
Chao-Wen Lin 1,  Shang-Chih Yang 2,  Vladlen Klochkov 2,  Ta-Ching Chen 3,  Wei-Kai Huang 4,  Wei-Li Chen 5
Affiliations

Affiliations

  • 1 Department of Ophthalmology, National Taiwan University Hospital, Taipei, Taiwan.
  • 2 Department of Ophthalmology, National Taiwan University College of Medicine, Taipei, Taiwan.
  • 3 Department of Ophthalmology, National Taiwan University Hospital, Taipei, Taiwan; Center of Frontier Medicine, National Taiwan University Hospital, Taipei, Taiwan.
  • 4 Department of Ophthalmology, National Taiwan University College of Medicine, Taipei, Taiwan; Genomics Research Center, Academia Sinica, Taipei, Taiwan.
  • 5 Department of Ophthalmology, National Taiwan University Hospital, Taipei, Taiwan. Electronic address: chenweili@ntu.edu.tw.
PMID: 40409357 DOI: 10.1016/j.exer.2025.110440
Abstract

Retinal ganglion cell degeneration is the main cause of irreversible vision loss in optic neuropathies. Pigment epithelium-derived factor (PEDF) and its smaller peptide components (44-mer and 17-mer) have shown neuroprotective effects. In this study, using a stepwise protocol we investigated their effects on human-induced pluripotent stem cell differentiation to retinal ganglion cells. Various concentrations of PEDF, 44-mer and 17-mer were added at day 18. Investigated compounds significantly upregulated the expression of retinal ganglion cells-specific (Brn3b, Sncg), retinal progenitor (Pax6) and neuroaxonal markers (Tau, NFH). They also highly increased Brn3b expression, as well as neurite length and density, supporting their neurotrophic properties. Our findings suggest that PEDF and its smaller peptide components, 44-mer and 17-mer, can be suggested as neuroprotective agents for the promotion of retinal ganglion cell differentiation from human-induced pluripotent stem cells. 44-mer and 17-mer have comparable or even higher effects to full-length PEDF and might also bypass PEDF usage limitations.

Keywords

Differentiation; Neuroprotection; Optic neuropathy; PEDF; RGC; iPSC.

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