Upregulation of the vascular endothelial growth factor/vascular endothelial growth factor receptor system in experimental background diabetic retinopathy of the rat

Hans Peter Hammes, Jihong Lin, Reinhard G. Bretzel, Michael Brownlee, Georg Breier

Research output: Contribution to journalArticle

212 Citations (Scopus)

Abstract

Vascular endothelial growth factor (VEGF) is a major contributor to retinal neovascularization. The possible participation of VEGF and its high- affinity tyrosine kinase receptors, flk-1 and flt-1, in early background diabetic retinopathy was studied in the streptozotocin-induced diabetic rat model of experimental retinopathy using in situ hybridization, blotting techniques, and immunohistochemistry. Diabetic retinopathy was assessed by quantitative morphometry of retinal digest preparations. The number of acellular capillaries increased 2.7-fold in diabetic animals with diabetes' duration of 6 months compared with nondiabetic controls. VEGF expression was not detectable by in situ hybridization in nondiabetic rats but was highly increased in the ganglion cell layer and in the inner and outer nuclear layers of retinas from diabetic animals. VEGF protein was extractable only from diabetic retinas, and a strong immunolabeling was detected in vascular and perivascular structures. Increased flk-1 and flt-1 mRNA levels were also found in the ganglion cell and both nuclear layers of diabetic samples only. Dot blot and Western blot analyses confirmed the increase in flk-1 mRNA and protein in diabetic retinas. Also, flk-1 immunoreactivity was associated with vascular and nonvascular structures of the inner retinas from diabetic animals. These data obtained from a rodent model in which retinal neovascularization does not occur support the concept that the VEGF/VEGF receptor system is upregulated in early diabetic retinopathy.

Original languageEnglish (US)
Pages (from-to)401-406
Number of pages6
JournalDiabetes
Volume47
Issue number3
DOIs
StatePublished - 1998

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Vascular Endothelial Growth Factor Receptor
Diabetic Retinopathy
Vascular Endothelial Growth Factor A
Up-Regulation
Retina
Retinal Neovascularization
Vascular Endothelial Growth Factor Receptor-2
Ganglia
In Situ Hybridization
Blood Vessels
Messenger RNA
Streptozocin
Rodentia
Theoretical Models
Western Blotting
Immunohistochemistry
Proteins

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Upregulation of the vascular endothelial growth factor/vascular endothelial growth factor receptor system in experimental background diabetic retinopathy of the rat. / Hammes, Hans Peter; Lin, Jihong; Bretzel, Reinhard G.; Brownlee, Michael; Breier, Georg.

In: Diabetes, Vol. 47, No. 3, 1998, p. 401-406.

Research output: Contribution to journalArticle

Hammes, Hans Peter ; Lin, Jihong ; Bretzel, Reinhard G. ; Brownlee, Michael ; Breier, Georg. / Upregulation of the vascular endothelial growth factor/vascular endothelial growth factor receptor system in experimental background diabetic retinopathy of the rat. In: Diabetes. 1998 ; Vol. 47, No. 3. pp. 401-406.
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