Virchows Archiv

, Volume 426, Issue 5, pp 479–486 | Cite as

Hypoxia-induced expression of vascular endothelial growth factor by retinal glial cells promotes in vitro angiogenesis

  • Y. Hata
  • K. Nakagawa
  • K. Sueishi
  • T. Ishibashi
  • H. Inomata
  • H. Ueno
Original Article

Abstract

To determine whether retinal glial cells (RGCs) participate in the paracrine regulation of retinal neovascularization, we investigated whether cultured RGCs synthesize and release vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) under normoxic or hypoxic conditions. Northern blot analysis demonstrated that cultured RGCs transcribed both VEGF mRNA with two molecular bands approximately 3.9 and 4.3 kilobases (kb), and bFGF mRNA with approximately 3.7 and 6.0 kb. The expression of VEGF mRNA was greatly enhanced by hypoxic cultivation (2% oxygen) when compared with normoxic cultivation (20% oxygen), while the expression of bFGF mRNA by RGCs was not significantly affected by hypoxia. The effects of RGCs-conditioned media (CM) on tritiated-thymidine incorporation and in vitro angiogenesis by retinal capillary endothelial cells (RECs) in producing the formation of capillary-like tubes in type I collagen gels, were evident in the observation that RGCs-CM harvested after hypoxic cultivation significantly enhanced tritiated-thymidine incorporation (1.9 times, P<0.01) and in vitro angiogenesis (2.4 times, P<0.01) compared with the normoxic RGCs-CM. These enhancing effects of RGCs-CM at hypoxia were suppressed by anti-VEGF neutralizing antibody. Furthermore, RECs were shown to express mRNA encoding the VEGF receptor flt-1 by northern blot analysis. These results suggest that VEGF expressed by RGCs under hypoxic conditions plays an integral role in the initiation and progression of retinal neovascularization in a paracrine manner.

Key words

Vascular endothelial growth factor Retinal glial cells Hypoxia Angiogenesis Retinal capillary endothelial cells 

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Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • Y. Hata
    • 2
  • K. Nakagawa
    • 1
  • K. Sueishi
    • 1
  • T. Ishibashi
    • 2
  • H. Inomata
    • 2
  • H. Ueno
    • 3
  1. 1.Department of Pathology 1, Faculty of MedicineKyushu University 60FukuokaJapan
  2. 2.Department of Ophthalmology, Faculty of MedicineKyushu UniversityFukuokaJapan
  3. 3.Department of Cardiology, Faculty of MedicineKyushu UniversityFukuokaJapan

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