The role of inverted internal limiting membrane flap in macular hole closure

Yusuke Shiode, Yuki Morizane, Ryo Matoba, Masayuki Hirano, Shinichiro Doi, Shinji Toshima, Kosuke Takahashi, Ryoichi Araki, Yuki Kanzaki, Mika Hosogi, Tomoko Yonezawa, Atsushi Yoshida, Fumio Shiraga

Research output: Contribution to journalArticlepeer-review

128 Citations (Scopus)


PURPOSE. To investigate the mechanism of macular hole (MH) closure following the inverted internal limiting membrane (ILM) technique. METHODS. We performed the inverted ILM flap surgical technique as an experimental MH model in monkeys, and investigated the process of MH closure immunohistochemically. We then investigated the effects of type IV collagen, fibronectin, and laminin, which are constituent proteins of the ILM, on the proliferation and migration of cultivated Müller cells (MIO-M1). We also investigated the expression of neurotrophic factors and basic fibroblast growth factor (bFGF) in human ILM and MIO-M1 cells, and the effect of MIO-M1 migration on the expression of these factors, via immunohistochemical staining and the real-time reverse transcription polymerase chain reaction. RESULTS. Ten days after inverted ILM flap surgery, the MH had closed and proliferating glial fibrillary acidic protein (GFAP)-positive cells surrounded the ILM. Type IV collagen, fibronectin, and laminin all enhanced the proliferation of MIO-M1 cells, and type IV collagen and fibronectin enhanced the migration of MIO-M1 cells. Neurotrophic factors and bFGF were present on the surface of the human ILM, and MIO-M1 cells produced these factors. Neurotrophic factors and bFGF were expressed to a significantly greater extent by migrating MIO-M1 cells than by these cells in their static state. CONCLUSIONS. During MH closure, the ILM functioned as a scaffold for the proliferation and migration of Müller cells, and may promote Müller cell activation. Neurotrophic factors and bFGF produced by activated Müller cells and present on the surface of the ILM may contribute to MH closure.

Original languageEnglish
Pages (from-to)4847-4855
Number of pages9
JournalInvestigative Ophthalmology and Visual Science
Issue number11
Publication statusPublished - Sept 2017


  • Internal limiting membrane
  • Macular hole
  • Müller cell

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience


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