Endothelial and glial cell interaction in diabetic retinopathy via the function of vascular endothelial growth factor (VEGF)

Katsuo Sueishi, Yasuaki Hata, Toshinori Murata, Kazunori Nakagawa, Tatsuro Ishibashi, Hajime Inomata

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21 Citations (Scopus)


VEGF, which is also known as vascular permeability factor (VPF), is a recently identified specific mitogen for endothelial cells, and has been paid much attention for the critical participation in the physiological and pathological angiogenesis/vasculogenesis in retinas. To investigate whether retinal glial cells (RGCs) synthesize VEGF under hypoxic state (2%) in vitro and in retinas in vivo of streptozotocin-induced diabetic rats, VEGF mRNA and activity expressed by cultured RGCs were assessed with Northern blot analysis and in vitro angiogenesis assay, and the in vivo expression of VEGF mRNA and protein was examined in diabetic retinas by in situ hybridization and immunohistochemistry using rabbit anti-IgG against human VEGE Cultured RGCs synthesized and released VEGF and this VEGF production was markedly enhanced by hypoxia through the activation of AP-1 promotor gene. However, the expression of bFGF mRNA by RGCs was not enhanced under the hypoxic condition. Retinal capillary endothelial cells (RECs) expressed fit-1 mRNA. Therefore, conditioned media harvested from RGCs under hypoxic condition significantly accelerated not only thymidine incorporation by RECs but also in vitro angiogenesis, namely, the formation of capillary-like tubes by RECs in type I collagen gels. In normal rat retinas astrocytes located just beneath the inner limiting membrane revealed immunohistochemically the weak expression of VEGF, while in diabetic retinas six months after the streptozotocin treatment, the enhanced expression of VEGF mRNA and protein mainly by glial cells such as Muller cells and astrocytes, was confirmed by immunohistochemistry and in situ hybridization. These diabetic retinas were associated with the hyperpermeability of albumin, but not angiogenic retinopathy. These findings indicate that VEGF expressed by RGCs under hypoxia or diabetic condition plays an integral role in the maintenance of retinal circulation via the VEGF-VEGF receptor (fit-1) interaction.

Original languageEnglish
Pages (from-to)307-316
Number of pages10
JournalPolish Journal of Pharmacology
Issue number3
Publication statusPublished - Sept 17 1996

All Science Journal Classification (ASJC) codes

  • Pharmacology


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