Cellular migration associated with macular hole: A new method for comprehensive bird's-eye analysis of the internal limiting membrane

Toshio Hisatomi, Hiroshi Enaida, Taiji Sakamoto, Takaaki Kanemaru, Tadahisa Kagimoto, Ichiro Yamanaka, Akifumi Ueno, Takao Nakamura, Yasuaki Hata, Tatsuro Ishibashi

Research output: Contribution to journalReview article

29 Citations (Scopus)

Abstract

Objective: To elucidate the pathogenesis of macular hole formation, focusing in particular on the possible role of cellular migration on the cortical vitreous and internal limiting membrane (ILM) around the macular hole. Methods: To gain a comprehensive overview of the ILM excised in macular hole surgery (n=36), the ILMs were carefully unfolded and spread out onto glass slides as continuous flat sheets that each contained a macular hole. The specimens were observed by light microscopy and transmission electron microscopy (n=9), and the cellular distribution was analyzed by scanning electron microscopy in a quantitative manner (n=27). Immunohistochemistry for glial fibrillary acidic protein and cytokeratin 18 was carried out for cellular characterization. Cellular proliferation was assessed by immunohistochemistry for proliferating cell nuclear antigen and Ki-67. Results: Cellular migration was not apparent around the macular hole in the early stage of development of the macular hole (stage 2, 0 μm). As the macular hole passed through the later stages of development, cellular migration developed around the macular hole (stage 3, 84 μm) and the area of cellular migration gradually enlarged (stage 4, 420 μm). The immunophenotypic analysis showed that these cells were mainly glial fibrillary acidic protein-positive glial cells and cytokeratin 18-positive retinal pigment epithelial cells. The proliferating cell nuclear antigen and Ki-67 immunohistochemistry showed that some of these cells were proliferating on the ILM. Conclusions: Cellular migration on the ILM is not necessary for the initial formation of a macular break. Cellular migration developed after the macular break occurred, and the migration and proliferation increased gradually from the macular hole. Clinical Relevance: This study provides a new method for understanding the ultrastructural analysis of the pathogenesis of the macular hole.

Original languageEnglish
Pages (from-to)1005-1011
Number of pages7
JournalArchives of Ophthalmology
Volume124
Issue number7
DOIs
Publication statusPublished - Jul 17 2006

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Retinal Perforations
Birds
Membranes
Keratin-18
Immunohistochemistry
Glial Fibrillary Acidic Protein
Proliferating Cell Nuclear Antigen
Retinal Pigments
Transmission Electron Microscopy
Neuroglia
Electron Scanning Microscopy
Glass
Microscopy
Epithelial Cells
Cell Proliferation
Light

All Science Journal Classification (ASJC) codes

  • Ophthalmology

Cite this

Cellular migration associated with macular hole : A new method for comprehensive bird's-eye analysis of the internal limiting membrane. / Hisatomi, Toshio; Enaida, Hiroshi; Sakamoto, Taiji; Kanemaru, Takaaki; Kagimoto, Tadahisa; Yamanaka, Ichiro; Ueno, Akifumi; Nakamura, Takao; Hata, Yasuaki; Ishibashi, Tatsuro.

In: Archives of Ophthalmology, Vol. 124, No. 7, 17.07.2006, p. 1005-1011.

Research output: Contribution to journalReview article

Hisatomi, T, Enaida, H, Sakamoto, T, Kanemaru, T, Kagimoto, T, Yamanaka, I, Ueno, A, Nakamura, T, Hata, Y & Ishibashi, T 2006, 'Cellular migration associated with macular hole: A new method for comprehensive bird's-eye analysis of the internal limiting membrane', Archives of Ophthalmology, vol. 124, no. 7, pp. 1005-1011. https://doi.org/10.1001/archopht.124.7.1005
Hisatomi, Toshio ; Enaida, Hiroshi ; Sakamoto, Taiji ; Kanemaru, Takaaki ; Kagimoto, Tadahisa ; Yamanaka, Ichiro ; Ueno, Akifumi ; Nakamura, Takao ; Hata, Yasuaki ; Ishibashi, Tatsuro. / Cellular migration associated with macular hole : A new method for comprehensive bird's-eye analysis of the internal limiting membrane. In: Archives of Ophthalmology. 2006 ; Vol. 124, No. 7. pp. 1005-1011.
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abstract = "Objective: To elucidate the pathogenesis of macular hole formation, focusing in particular on the possible role of cellular migration on the cortical vitreous and internal limiting membrane (ILM) around the macular hole. Methods: To gain a comprehensive overview of the ILM excised in macular hole surgery (n=36), the ILMs were carefully unfolded and spread out onto glass slides as continuous flat sheets that each contained a macular hole. The specimens were observed by light microscopy and transmission electron microscopy (n=9), and the cellular distribution was analyzed by scanning electron microscopy in a quantitative manner (n=27). Immunohistochemistry for glial fibrillary acidic protein and cytokeratin 18 was carried out for cellular characterization. Cellular proliferation was assessed by immunohistochemistry for proliferating cell nuclear antigen and Ki-67. Results: Cellular migration was not apparent around the macular hole in the early stage of development of the macular hole (stage 2, 0 μm). As the macular hole passed through the later stages of development, cellular migration developed around the macular hole (stage 3, 84 μm) and the area of cellular migration gradually enlarged (stage 4, 420 μm). The immunophenotypic analysis showed that these cells were mainly glial fibrillary acidic protein-positive glial cells and cytokeratin 18-positive retinal pigment epithelial cells. The proliferating cell nuclear antigen and Ki-67 immunohistochemistry showed that some of these cells were proliferating on the ILM. Conclusions: Cellular migration on the ILM is not necessary for the initial formation of a macular break. Cellular migration developed after the macular break occurred, and the migration and proliferation increased gradually from the macular hole. Clinical Relevance: This study provides a new method for understanding the ultrastructural analysis of the pathogenesis of the macular hole.",
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AU - Kanemaru, Takaaki

AU - Kagimoto, Tadahisa

AU - Yamanaka, Ichiro

AU - Ueno, Akifumi

AU - Nakamura, Takao

AU - Hata, Yasuaki

AU - Ishibashi, Tatsuro

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N2 - Objective: To elucidate the pathogenesis of macular hole formation, focusing in particular on the possible role of cellular migration on the cortical vitreous and internal limiting membrane (ILM) around the macular hole. Methods: To gain a comprehensive overview of the ILM excised in macular hole surgery (n=36), the ILMs were carefully unfolded and spread out onto glass slides as continuous flat sheets that each contained a macular hole. The specimens were observed by light microscopy and transmission electron microscopy (n=9), and the cellular distribution was analyzed by scanning electron microscopy in a quantitative manner (n=27). Immunohistochemistry for glial fibrillary acidic protein and cytokeratin 18 was carried out for cellular characterization. Cellular proliferation was assessed by immunohistochemistry for proliferating cell nuclear antigen and Ki-67. Results: Cellular migration was not apparent around the macular hole in the early stage of development of the macular hole (stage 2, 0 μm). As the macular hole passed through the later stages of development, cellular migration developed around the macular hole (stage 3, 84 μm) and the area of cellular migration gradually enlarged (stage 4, 420 μm). The immunophenotypic analysis showed that these cells were mainly glial fibrillary acidic protein-positive glial cells and cytokeratin 18-positive retinal pigment epithelial cells. The proliferating cell nuclear antigen and Ki-67 immunohistochemistry showed that some of these cells were proliferating on the ILM. Conclusions: Cellular migration on the ILM is not necessary for the initial formation of a macular break. Cellular migration developed after the macular break occurred, and the migration and proliferation increased gradually from the macular hole. Clinical Relevance: This study provides a new method for understanding the ultrastructural analysis of the pathogenesis of the macular hole.

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