Blood-retinal barrier breakdown induced by activation of protein kinase C via vascular endothelial growth factor in streptozotocin-induced diabetic rats.
OBJECTIVE
To investigate (1) the mechanism of blood-retinal barrier breakdown induced by protein kinase C (PKC) activation (2) the relationship between PKC activation and vascular endothelial growth factor (VEGF) in 2-week streptozotocin-induced diabetes.


METHODS
Retinal PKC activities, retinal and vitreous concentration of VEGF protein were conducted by enzyme-linked immunoabsorbent assay (ELISA). Retinal VEGF mRNA expression was analyzed by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). Blood-retinal barrier breakdown was quantified using the Evans blue technique. Alteration of retinal VEGF and blood-retinal barrier were observed after intravitreal injection of PKC inhibitor, GF109203X, in 2-week diabetic rats.


RESULTS
Two weeks of diabetes in rats resulted in elevation of retinal PKC specific activities, retinal and vitreous VEGF, and retinal vascular permeability. Retinal VEGF and retinal vascular permeability were decreased after intravitreal injection of GF109203X (10(-5), 10(-6) mol/L) in a dose-dependent manner.


CONCLUSIONS
The results from this study showed that enhanced expression of VEGF and PKC in early diabetes and the blood-retinal barrier breakdown of early diabetic retinopathy induced by PKC activation may be partly due to the upregulation of VEGF. PKC inhibitor could reverse the blood-retinal barrier breakdown.
Xu
Xun
X
Department of Ophthalmology, Shanghai First People's Hospital, Shanghai, People's Republic of China. maxzhu@public7.sta.net.cn
Zhu
Qi
Q
Xia
Xin
X
Zhang
Shijie
S
Gu
Qing
Q
Luo
Dawei
D
D000818:Animals; D001813:Blood-Retinal Barrier; D002199:Capillary Permeability; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology*; D003930:Diabetic Retinopathy / Q000201:enzymology*; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008301:Maleimides / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000201:enzymology; D012171:Retinal Vessels / Q000201:enzymology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*; D014822:Vitreous Body / Q000201:enzymology
D004791:Enzyme Inhibitors; D007211:Indoles; D008301:Maleimides; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D011493:Protein Kinase C; C070515:bisindolylmaleimide I