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Retinal heparanase expression in streptozotocin-induced diabetic rats. 2010

Pingping Ma, and Yan Luo, and Xiaobo Zhu, and Tao Li, and Jie Hu, and Shibo Tang
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.

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.

UI MeSH Term Description Entries
D007150 Immunohistochemistry Histochemical localization of immunoreactive substances using labeled antibodies as reagents. Immunocytochemistry,Immunogold Techniques,Immunogold-Silver Techniques,Immunohistocytochemistry,Immunolabeling Techniques,Immunogold Technics,Immunogold-Silver Technics,Immunolabeling Technics,Immunogold Silver Technics,Immunogold Silver Techniques,Immunogold Technic,Immunogold Technique,Immunogold-Silver Technic,Immunogold-Silver Technique,Immunolabeling Technic,Immunolabeling Technique,Technic, Immunogold,Technic, Immunogold-Silver,Technic, Immunolabeling,Technics, Immunogold,Technics, Immunogold-Silver,Technics, Immunolabeling,Technique, Immunogold,Technique, Immunogold-Silver,Technique, Immunolabeling,Techniques, Immunogold,Techniques, Immunogold-Silver,Techniques, Immunolabeling
D008297 Male Males
D009844 Oligosaccharides Carbohydrates consisting of between two (DISACCHARIDES) and ten MONOSACCHARIDES connected by either an alpha- or beta-glycosidic link. They are found throughout nature in both the free and bound form. Oligosaccharide
D012160 Retina The ten-layered nervous tissue membrane of the eye. It is continuous with the OPTIC NERVE and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the CHOROID and the inner surface with the VITREOUS BODY. The outer-most layer is pigmented, whereas the inner nine layers are transparent. Ora Serrata
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D003921 Diabetes Mellitus, Experimental Diabetes mellitus induced experimentally by administration of various diabetogenic agents or by PANCREATECTOMY. Alloxan Diabetes,Streptozocin Diabetes,Streptozotocin Diabetes,Experimental Diabetes Mellitus,Diabete, Streptozocin,Diabetes, Alloxan,Diabetes, Streptozocin,Diabetes, Streptozotocin,Streptozocin Diabete
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004730 Endothelium, Vascular Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components. Capillary Endothelium,Vascular Endothelium,Capillary Endotheliums,Endothelium, Capillary,Endotheliums, Capillary,Endotheliums, Vascular,Vascular Endotheliums
D004797 Enzyme-Linked Immunosorbent Assay An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed. ELISA,Assay, Enzyme-Linked Immunosorbent,Assays, Enzyme-Linked Immunosorbent,Enzyme Linked Immunosorbent Assay,Enzyme-Linked Immunosorbent Assays,Immunosorbent Assay, Enzyme-Linked,Immunosorbent Assays, Enzyme-Linked
D005947 Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Dextrose,Anhydrous Dextrose,D-Glucose,Glucose Monohydrate,Glucose, (DL)-Isomer,Glucose, (alpha-D)-Isomer,Glucose, (beta-D)-Isomer,D Glucose,Dextrose, Anhydrous,Monohydrate, Glucose

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