TEM7 (PLXDC1) in neovascular endothelial cells of fibrovascular membranes from patients with proliferative diabetic retinopathy

Yoko Yamaji, Shigeo Yoshida, Keijiro Ishikawa, Akihito Sengoku, Kota Sato, Ayako Yoshida, Rumi Kuwahara, Kenoki Ohuchida, Eiji Oki, Hiroshi Enaida, Kimihiko Fujisawa, Toshihiro Kono, Tatsuro Ishibashi

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

PURPOSE. Proliferative diabetic retinopathy (PDR) results from the formation of fibrovascular membranes (FVMs) in the posterior fundus that can lead to a severe decrease of vision. Tumor endothelial marker 7 (TEM7) is a protein that is highly expressed in the endothelial cells of tumors, but whether it plays a role in FVMs is unknown. The purpose of this study was to determine whether TEM7 is associated with the formation of FVMs. METHODS. FVMs were obtained during vitrectomy from patients with PDR. RT-PCR was performed to determine the level of expression of the mRNA of TEM7. The splice variants of TEM7 were identified by direct sequencing. Immunohistochemical analyses and in situ hybridization was performed to determine the sites of TEM7 in the FVMs. RESULTS. The level of the mRNA of TEM7 was high in 10 of 10 FVMs but was barely detectable in the five idiopathic epiretinal membranes. Direct sequencing of subcloned TEM7 PCR products revealed several splice variants (intracellular, secreted, and membrane-bound forms of TEM7) in the FVMs. Immunohistochemical analysis showed a colocalization of TEM7 and CD34, an endothelial cell marker, in most of the neovascular endothelial cells in the FVMs. Immunoelectron microscopy revealed that membrane-bound TEM7 was expressed on the luminal surfaces of the vascular endothelial cells of FVMs. CONCLUSIONS. This study indicates that TEM7 may play a significant role in the proliferation and maintenance of neovascular endothelial cells in the FVMs. If correct, TEM7 may be a molecular target for new diagnostic and therapeutic strategies for PDR.

Original languageEnglish
Pages (from-to)3151-3157
Number of pages7
JournalInvestigative Ophthalmology and Visual Science
Volume49
Issue number7
DOIs
Publication statusPublished - Jul 1 2008

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Diabetic Retinopathy
Tumor Biomarkers
Endothelial Cells
Cell Membrane
Membranes
Epiretinal Membrane
Polymerase Chain Reaction
Intracellular Membranes
Messenger RNA
Immunoelectron Microscopy
Vitrectomy
In Situ Hybridization
Maintenance

All Science Journal Classification (ASJC) codes

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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TEM7 (PLXDC1) in neovascular endothelial cells of fibrovascular membranes from patients with proliferative diabetic retinopathy. / Yamaji, Yoko; Yoshida, Shigeo; Ishikawa, Keijiro; Sengoku, Akihito; Sato, Kota; Yoshida, Ayako; Kuwahara, Rumi; Ohuchida, Kenoki; Oki, Eiji; Enaida, Hiroshi; Fujisawa, Kimihiko; Kono, Toshihiro; Ishibashi, Tatsuro.

In: Investigative Ophthalmology and Visual Science, Vol. 49, No. 7, 01.07.2008, p. 3151-3157.

Research output: Contribution to journalArticle

Yamaji, Yoko ; Yoshida, Shigeo ; Ishikawa, Keijiro ; Sengoku, Akihito ; Sato, Kota ; Yoshida, Ayako ; Kuwahara, Rumi ; Ohuchida, Kenoki ; Oki, Eiji ; Enaida, Hiroshi ; Fujisawa, Kimihiko ; Kono, Toshihiro ; Ishibashi, Tatsuro. / TEM7 (PLXDC1) in neovascular endothelial cells of fibrovascular membranes from patients with proliferative diabetic retinopathy. In: Investigative Ophthalmology and Visual Science. 2008 ; Vol. 49, No. 7. pp. 3151-3157.
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T1 - TEM7 (PLXDC1) in neovascular endothelial cells of fibrovascular membranes from patients with proliferative diabetic retinopathy

AU - Yamaji, Yoko

AU - Yoshida, Shigeo

AU - Ishikawa, Keijiro

AU - Sengoku, Akihito

AU - Sato, Kota

AU - Yoshida, Ayako

AU - Kuwahara, Rumi

AU - Ohuchida, Kenoki

AU - Oki, Eiji

AU - Enaida, Hiroshi

AU - Fujisawa, Kimihiko

AU - Kono, Toshihiro

AU - Ishibashi, Tatsuro

PY - 2008/7/1

Y1 - 2008/7/1

N2 - PURPOSE. Proliferative diabetic retinopathy (PDR) results from the formation of fibrovascular membranes (FVMs) in the posterior fundus that can lead to a severe decrease of vision. Tumor endothelial marker 7 (TEM7) is a protein that is highly expressed in the endothelial cells of tumors, but whether it plays a role in FVMs is unknown. The purpose of this study was to determine whether TEM7 is associated with the formation of FVMs. METHODS. FVMs were obtained during vitrectomy from patients with PDR. RT-PCR was performed to determine the level of expression of the mRNA of TEM7. The splice variants of TEM7 were identified by direct sequencing. Immunohistochemical analyses and in situ hybridization was performed to determine the sites of TEM7 in the FVMs. RESULTS. The level of the mRNA of TEM7 was high in 10 of 10 FVMs but was barely detectable in the five idiopathic epiretinal membranes. Direct sequencing of subcloned TEM7 PCR products revealed several splice variants (intracellular, secreted, and membrane-bound forms of TEM7) in the FVMs. Immunohistochemical analysis showed a colocalization of TEM7 and CD34, an endothelial cell marker, in most of the neovascular endothelial cells in the FVMs. Immunoelectron microscopy revealed that membrane-bound TEM7 was expressed on the luminal surfaces of the vascular endothelial cells of FVMs. CONCLUSIONS. This study indicates that TEM7 may play a significant role in the proliferation and maintenance of neovascular endothelial cells in the FVMs. If correct, TEM7 may be a molecular target for new diagnostic and therapeutic strategies for PDR.

AB - PURPOSE. Proliferative diabetic retinopathy (PDR) results from the formation of fibrovascular membranes (FVMs) in the posterior fundus that can lead to a severe decrease of vision. Tumor endothelial marker 7 (TEM7) is a protein that is highly expressed in the endothelial cells of tumors, but whether it plays a role in FVMs is unknown. The purpose of this study was to determine whether TEM7 is associated with the formation of FVMs. METHODS. FVMs were obtained during vitrectomy from patients with PDR. RT-PCR was performed to determine the level of expression of the mRNA of TEM7. The splice variants of TEM7 were identified by direct sequencing. Immunohistochemical analyses and in situ hybridization was performed to determine the sites of TEM7 in the FVMs. RESULTS. The level of the mRNA of TEM7 was high in 10 of 10 FVMs but was barely detectable in the five idiopathic epiretinal membranes. Direct sequencing of subcloned TEM7 PCR products revealed several splice variants (intracellular, secreted, and membrane-bound forms of TEM7) in the FVMs. Immunohistochemical analysis showed a colocalization of TEM7 and CD34, an endothelial cell marker, in most of the neovascular endothelial cells in the FVMs. Immunoelectron microscopy revealed that membrane-bound TEM7 was expressed on the luminal surfaces of the vascular endothelial cells of FVMs. CONCLUSIONS. This study indicates that TEM7 may play a significant role in the proliferation and maintenance of neovascular endothelial cells in the FVMs. If correct, TEM7 may be a molecular target for new diagnostic and therapeutic strategies for PDR.

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