Vascular endothelial growth factor- and platelet-derived growth factor-angiogenesis depressed but fetal bovine serum-angiogenesis enhanced choroidal tissue cultures of streptozotocin-diabetic Wistar and GK rats.
BACKGROUND
Diabetic state-induced alterations of angiogenic activity of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) were compared with that of fetal bovine serum (FBS) in the cultured choroidal explants of streptozotocin (STZ)-diabetic Wistar and diabetic GK rats.


METHODS
Choroidal explants (0.04-1.0 mm2) were isolated from rat eyeballs and cultured in fibrin gels with FBS-Dulbecco's modified Eagle's medium (0.5 mL) containing antibiotics and 300 microg/mL epsilon-amino caproic acid in the presence of recombinant mouse vascular endothelial growth factor and recombinant human platelet-derived growth factor BB at 37 degrees C under 5% CO2 and 95% air. Microvessels newly budded from these choroidal explants were photographed. The number and length of all microvessels per choroidal explant were counted and measured as indices of angiogenesis in vitro.


RESULTS
Fetal bovine serum (5-10%) enhanced both angiogenic indices in the explants of STZ-diabetic Wistar and GK rats. The actions of the serum on both angiogenic indices in both diabetic rats were greater than those in age-matched normal rats. Vascular endothelial growth factor (3-30 ng/mL) with 1% fetal bovine serum increased the angiogenic indices in diabetic choroids, but was less pronounced than in normal choroids. The action of the growth factor (2.5 ng/mL) on angiogenesis was also less in diabetic choroids.


CONCLUSIONS
Results suggest that the diabetic state may down-regulate the receptors for vascular endothelial and platelet-derived growth factors and/or desensitize their post-receptor signaling in the vascular endothelial cells of choroids, being inexplicable for the enhanced actions of fetal bovine serum on angiogenesis in diabetic choroids.
Kimura
I
I
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Sugitani, Japan.
Yanagita
S
S
Kobayshi
S
S
Fukuta
M
M
Okabe
M
M
D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity; D002452:Cell Count; D002829:Choroid / Q000187:drug effects / Q000473:pathology*; D020256:Choroidal Neovascularization / Q000209:etiology / Q000473:pathology* / Q000517:prevention & control; D003470:Culture Media / Q000494:pharmacology; D046508:Culture Techniques; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000150:complications* / Q000473:pathology; D016228:Endothelial Growth Factors / Q000494:pharmacology*; D005312:Fetal Blood; D008222:Lymphokines / Q000494:pharmacology*; D008297:Male; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D020033:Protein Isoforms / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin / Q000633:toxicity; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000900:Anti-Bacterial Agents; D003470:Culture Media; D016228:Endothelial Growth Factors; D008222:Lymphokines; D010982:Platelet-Derived Growth Factor; D020033:Protein Isoforms; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D013311:Streptozocin