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Peer-reviewedCC BY 4.0Cells

Establishment and Characterization of TGFBI R124L iPSCs Derived from a Reis–Bücklers Corneal Dystrophy Family

  • Momoko Kawasaki-Takahashi1
  • Ryo Tomemori1
  • Yoshikazu Matsuoka2
  • Tatsuya Kanagawa2
  • Yoshiki Yasukochi3
  • Koichiro Higasa3
  • Hisanori Imai1
  • Kaoru Araki-Sasaki1
  • Hirofumi Hitomi2
  1. 1Department of Ophthalmology, Kansai Medical University, Hirakata 573-1010, Osaka, Japan
  2. 2Department of iPS Stem Cell Regenerative Medicine, Kansai Medical University, Hirakata 573-1010, Osaka, Japan
  3. 3Department of Genome Analysis, Institute of Biomedical Science, Kansai Medical University, Hirakata 573-1010, Osaka, Japan
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Abstract

Reis–Bücklers corneal dystrophy (RBCD) is an early-onset TGFBI-related corneal dystrophy associated with the TGFBI R124L variant. It is characterized by recurrent corneal epithelial erosion, hyaline-like deposits involving Bowman’s layer and the anterior stroma, and progressive subepithelial corneal opacity. However, how mutant TGFBI protein (TGFBIp) accumulates in the cornea remains unclear. In this study, we established induced pluripotent stem cells (iPSCs) from two affected members of an RBCD family and one unaffected family member. The patient-derived lines retained the R124L variant, whereas the line established from the unaffected mother did not. All three lines showed pluripotency and trilineage differentiation, had normal karyotypes, and were confirmed by STR analysis to match their donors. After 4 weeks of SEAM induction, all three iPSC lines developed early SEAM-like cultures containing PAX6- and p63-positive cells, demonstrating their capacity for early differentiation toward the corneal epithelial lineage. TGFBIp was also detected in extracellular and pericellular regions by immunofluorescence. In silico analysis detected no major structural difference between WT and R124L TGFBIp in the high-confidence CROPT and FAS1 domain regions, whereas surface analysis showed local changes in electrostatic potential and molecular lipophilicity around residue 124. These lines can be used to study TGFBIp deposition and epithelial–stromal interactions in RBCD.

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Cite

BibTeXRIS
BibTeX
@article{kawasakitakahashi2026establishment,
  title = {{Establishment and Characterization of TGFBI R124L iPSCs Derived from a Reis–Bücklers Corneal Dystrophy Family}},
  author = {Momoko Kawasaki-Takahashi and Ryo Tomemori and Yoshikazu Matsuoka and Tatsuya Kanagawa and Yoshiki Yasukochi and Koichiro Higasa and Hisanori Imai and Kaoru Araki-Sasaki and Hirofumi Hitomi},
  journal = {Cells},
  year = {2026},
  month = nov,
  doi = {10.3390/cells15212025},
  url = {https://www.mdpi.com/2073-4409/15/21/2025},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Establishment and Characterization of TGFBI R124L iPSCs Derived from a Reis–Bücklers Corneal Dystrophy Family
AU  - Momoko Kawasaki-Takahashi
AU  - Ryo Tomemori
AU  - Yoshikazu Matsuoka
AU  - Tatsuya Kanagawa
AU  - Yoshiki Yasukochi
AU  - Koichiro Higasa
AU  - Hisanori Imai
AU  - Kaoru Araki-Sasaki
AU  - Hirofumi Hitomi
PY  - 2026
DA  - 2026/11/06
JO  - Cells
DO  - 10.3390/cells15212025
UR  - https://www.mdpi.com/2073-4409/15/21/2025
AB  - Reis–Bücklers corneal dystrophy (RBCD) is an early-onset TGFBI-related corneal dystrophy associated with the TGFBI R124L variant. It is characterized by recurrent corneal epithelial erosion, hyaline-like deposits involving Bowman’s layer and the anterior stroma, and progressive subepithelial corneal opacity. However, how mutant TGFBI protein (TGFBIp) accumulates in the cornea remains unclear. In this study, we established induced pluripotent stem cells (iPSCs) from two affected members of an RBCD family and one unaffected family member. The patient-derived lines retained the R124L variant, whereas the line established from the unaffected mother did not. All three lines showed pluripotency and trilineage differentiation, had normal karyotypes, and were confirmed by STR analysis to match their donors. After 4 weeks of SEAM induction, all three iPSC lines developed early SEAM-like cultures containing PAX6- and p63-positive cells, demonstrating their capacity for early differentiation toward the corneal epithelial lineage. TGFBIp was also detected in extracellular and pericellular regions by immunofluorescence. In silico analysis detected no major structural difference between WT and R124L TGFBIp in the high-confidence CROPT and FAS1 domain regions, whereas surface analysis showed local changes in electrostatic potential and molecular lipophilicity around residue 124. These lines can be used to study TGFBIp deposition and epithelial–stromal interactions in RBCD.
SN  - 2073-4409
ER  -