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- Title
Hyperglycemia Induces Retinal Connective Tissue Growth Factor Expression in Rats.
- Authors
Winkler, Jennifer L.; Kedees, Mamdouh H.; Guz, Yelena; Liu, Heng; Teitelman, Gladys
- Abstract
Diabetic retinopathy (DR) is a leading cause of blindness. Connective Tissue Growth Factor (CTGF) is a profibrotic factor shown to induce extracellular matrix production and angiogenesis. Vascular Endothelial Growth Factor (VEGF), linked to many of the vascular changes that occur in DR, induces CTGF in retinal pericytes and retinal endothelial cells. Our goal is to determine whether inhibition of CTGF could be beneficial for the treatment of DR. In this study we tested the effect of a recombinant adenovirus encoding for CTGF antisense oligonucleotide (rAdASO) on the levels of Transforming Growth Factor-b (TGF-b) induced CTGF expression in Rat 2 Fibroblasts. Using semi-quantitative RT-PCR, there was a two-fold increase in CTGF message induced by TGF-b in Rat 2 cells. Western blot (WB) and immunohistochemical (IHC) analysis revealed a two-fold increase in CTGF protein. This up-regulation of CTGF by TGF-b was inhibited by infection with rAdASO. These findings indicate that the viral treatment was effective in decreasing CTGF expression. Next we examined, whether CTGF expression increased during hyperglycemia in vivo. Sprague Dawley rats were made hyperglycemic by one IP injection of Streptozotocin (STZ, 80mg/kg). Rats with blood glucose (BG) levels greater than 350mg/dl were sacrificed at 4, 8 and 12 weeks after STZ treatment. Whole eyes and/or retinas were collected for semi-quantitative RT-PCR, WB and IHC. Twelve weeks after induction of hyperglycemia, CTGF message and protein increased two- and five-fold, respectively. IHC staining showed a dramatic increase in retinal staining for VEGF and for glial acidic fibrillary protein (GFAP), a marker of reactive astrocytes. These in vivo studies strongly suggest that hyperglycemia induces VEGF, GFAP and CTGF expression. Taken together, these findings demonstrate a possible use of CTGF as a target gene to ameliorate the pathological changes induced by DR.
- Publication
Diabetes, 2007, Vol 56, pA212
- ISSN
0012-1797
- Publication type
Academic Journal