Diabetes & Metabolism Journal

Original Articles

Vascular Endothelial Growth Factor (VEGF) and Advanced Glycation End Products (AGEs) Overexpression in the Retina and Serum and Lens Opacities of Streptozotocin-induced Diabetic Rats.: Young Sook Kim, Eun Jin Sohn, Chan Sik Kim, Yun Mi Lee, Dong Ho Jung, Nan Hee Kim, Hyun Young Lee, Jung Yeon Kim, Jin Sook Kim; Korean Diabetes J. 2008;32(1):44-52. Published online February 1, 2008; DOI: https://doi.org/10.4093/kdj.2008.32.1.44

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Abstract PDF: BACKGROUND
Vascular Endothelial Growth Factor (VEGF) and Advanced Glycation End products (AGEs) have been implicated in the development of diabetic retinopathy. In this study, we examined the expression of VEGF and AGEs in the retina and serum, apoptosis in the retina, and lens opacities in streptozotocin (STZ)-induced diabetic rats. METHODS: The localization of VEGF and AGEs in the retina of STZ-induced diabetic rats was determined by immunohistochemical analysis, and apoptotic cell death was assessed using the TUNEL assay. In the serum, STZ-induced diabetic rats were assayed for VEGF and AGEs by ELISA. Lenses were also isolated to detect the opacity. RESULTS: Expression of VEGF and accumulation of AGEs were significantly increased in the retinal ganglion cell layers (GCL) and nuclear cell layers (NCL) of STZ-induced diabetic rats compared to normal control rats. In addition to cellular expression, serum VEGF and AGEs levels were also increased significantly in STZ-diabetic rats compared to normal rats (both P < 0.001) and there was a significant correlation between the serum VEGF and AGEs levels (r = 0.504). The lens opaque density of STZ-induced diabetic rats were significantly higher than in normal rats (P < 0.001). CONCLUSIONS: AGEs could be involved in the development of diabetic retinopathy through the induction of VEGF. One could possibly correlate this lens opaque formation with elevation of AGE induced VEGF level. Thus, this study should be considered as a basic research for studying pathology of the retina and lens in diabetic experimental models.

Comparison of Minicircle with Conventional Plasmid for the Non-viral Vascular Endothelial Growth Factor (VEGF) Gene Therapy.: Minjeong Kwon, Soonhee Lee, Heysook Chung, Changshin Yoon, Mikyung Kim, Jeonghyun Park; Korean Diabetes J. 2007;31(6):465-471. Published online November 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.6.465

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Abstract PDF: BACKGROUND
Delayed wound healings in diabetic patients are related with the impairment of the expressions of various growth factors. Treatments using growth factors have been attempted on diabetic foot ulcer. VEGF (vascular endothelial growth factor) accelerates neo-angiogenesis on the early phase of the wound healing and exerts chemo-attractive effect for the other growth factors and cytokines. Non-viral gene transfer strategies are attractive tool for the gene therapy due to the safety and the versatility, but the low efficiency has been the serious problem. METHODS: We performed the VEGF gene therapy using reconstructed minicircle MINI-pbetaVEGF DNA with a polymeric carrier, polyethylenimine (PEI, 25 kDa) in HEK293, CHO, and NIH3T3 cell lines, and compared its efficiency with the conventional VEGF plasmid pbetaVEGF. RESULTS: The levels of expressed VEGF were higher in the groups using BPEI (branched PEI) as a gene carrier than naked plasmid transfer in all cell lines (P < 0.05). The minicircle MINI-pbetaVEGF DNA showed much higher VEGF expression than conventional plasmid pbetaVEGF (P < 0.05). CONCLUSION: Minicircle DNA MINI-pbetaVEGF showed much higher transfection efficiency than conventional plasmid pbetaVEGF. It might be used in actual human clinical trial due to its higher efficiency and possible safety for the treatment of diabetic foot ulcer.

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