Retinal heparanase expression in streptozotocin-induced diabetic rats.
OBJECTIVE
Heparanase, an endoglycosidase, exhibits strong proangiogenic capacity that can induce vascular endothelial growth factor (VEGF) expression in tumour angiogenesis. The purpose of this study was to evaluate heparanase expression and its relationship with VEGF in streptozotocin (STZ)-induced diabetic rats' retinas.


METHODS
Experimental study.


METHODS
STZ-induced rats and non-diabetic control rats.


METHODS
Heparanase expression was initially evaluated in cultured human retinal microvascular endothelial cells (HRECs) under high-glucose conditions by Western blot. Diabetes was induced in Sprague-Dawley rats by STZ intraperitoneal injection. Retinal heparanase expression was assayed in rats by immunohistochemistry. Heparanase inhibitor (phosphomannopentaose sulfate) was administrated to high-glucose-treated HRECs and diabetic rats. VEGF levels were evaluated in HRECs and retinas using enzyme-linked immunosorbent assay.


RESULTS
Heparanase expression was increased in HRECs under high-glucose conditions compared with controls (p < 0.01). Immunohistochemical studies indicated that heparanase signals were intense in the retinal vascular endothelia of diabetic rats, but faint in those of nondiabetic control rats. Quantitative analysis showed that heparanase protein expression was increased by 3.2-fold in diabetic rats' retinas compared with nondiabetic rats' retinas (p < 0.01). VEGF level was increased, as was heparanase expression, in high-glucose-treated HRECs and in the retinas of diabetic rats, and these increases were significantly decreased by phosphomannopentaose sulfate administration (p < 0.01).


CONCLUSIONS
Heparanase expression was upregulated and associated with an increase of VEGF expression in STZ-induced diabetic rat retinas. The data suggest that heparanase may be involved in the development of diabetic retinopathy and represents a possible novel target for therapeutic intervention.
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
Pingping
P
Ma
Yan
Y
Luo
Xiaobo
X
Zhu
Tao
T
Li
Jie
J
Hu
Shibo
S
Tang
D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology* / Q000378:metabolism / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005947:Glucose / Q000008:administration & dosage; D005966:Glucuronidase / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D009844:Oligosaccharides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000201:enzymology*; D012171:Retinal Vessels / Q000166:cytology / Q000201:enzymology; D012720:Severity of Illness Index; D013194:Staining and Labeling; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000378:metabolism; D000099175:Heparanase
D005947:Glucose; D005966:Glucuronidase; D009844:Oligosaccharides; D042461:Vascular Endothelial Growth Factor A; D000099175:Heparanase; C120158:phosphomannopentaose sulfate