Vascular endothelial growth factor and its receptors in control and diabetic rat eyes.
Vascular endothelial growth factor (VEGF) is an endothelial cell-specific angiogenic and permeability-inducing factor that has been implicated in the pathogenesis of diabetic retinopathy. In the present study, the localization and magnitude of VEGF, VEGF receptor-1 (VEGFR-1), and VEGF receptor-2 (VEGFR-2) gene expression were examined in the eye of streptozotocin-induced diabetic rats using quantitative in situ hybridization. VEGF protein was also examined by immunohistochemistry. Abundant VEGF mRNA and protein were present in the retinae of control rats. In the retinae of diabetic rats, VEGF gene expression was increased compared with control animals (p = 0.001). The increase in VEGF mRNA was noted in the ganglion cell layer and inner nuclear layer but not in the pigment epithelium of the retina. VEGF was also detected in blood vessels, ciliary body, and lens epithelium in both control and diabetic rats. The distributions of VEGFR-1 and VEGFR-2 were similar in both control and diabetic rats. VEGFR-1 mRNA was present beneath the inner limiting membrane and in the ganglion cell layer, inner nuclear layer, outer plexiform layer, and outer limiting membrane of the retina; it was also detected in blood vessels, the ciliary body, and the cornea. The magnitude and distribution of ocular VEGFR-1 mRNA were not affected by experimental diabetes. Expression of VEGFR-2 mRNA was noted in the inner nuclear layer and pigment epithelium of the retina and in blood vessels. An increase in VEGFR-2 mRNA in the diabetic retina was restricted to the inner nuclear layer. The presence of VEGF and its receptors in the control retina suggests a physiologic role for VEGF within the eye. The changes in retinal expression of VEGF and VEGFR-2 in association with diabetes suggest a role for this pathway in diabetic retinopathy.
Department of Medicine, Austin and Repatriation Medical Centre, West Heidelberg, Victoria, Australia.
R E
RE
Gilbert
D
D
Vranes
J L
JL
Berka
D J
DJ
Kelly
A
A
Cox
L L
LL
Wu
S A
SA
Stacker
M E
ME
Cooper
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology; D003930:Diabetic Retinopathy / Q000378:metabolism* / Q000473:pathology; D016228:Endothelial Growth Factors / Q000096:biosynthesis / Q000378:metabolism*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008222:Lymphokines / Q000096:biosynthesis / Q000378:metabolism*; D008297:Male; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000378:metabolism*; D017978:Receptors, Growth Factor / Q000096:biosynthesis / Q000378:metabolism*; D040262:Receptors, Vascular Endothelial Growth Factor; D012160:Retina / Q000378:metabolism* / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D011518:Proto-Oncogene Proteins; D017978:Receptors, Growth Factor; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1