Guzel Bikbova
Chiba University Graduate School of Medicine
Japan
Title: NF-kB and SP1 expression in AGEs exposed retina and influence of different neurotrophic factors on it
Biography
Biography: Guzel Bikbova
Abstract
Purpose: To determine the effect of advanced glycation end-products (AGEs) on neurite regeneration in isolated rat retinas and the regenerative affects of different neurotrophic factors. Furthermore, to examine whether nuclear factor-kB (NF-kB) and specificity protein 1 (SP1) expression are correlated with the regenerative effect of each neurotrophic factors. Methods: Retinal explants of 4 adult SD rats were three-dimensionally cultured in collagen gel and incubated in: 1. Serum free control culture media; 2. 100 μg/ml glucose-AGE-BSA, glycolaldehyde-AGE-BSA, glyceraldehyde-AGE-BSA media; 3. Glucose, glycol, glycer+100 ng/ml neurotrophin 4 (NT-4) media; 4. Glucose, glycol, glycer+100 ng/ml hepatocyte growth factor (HGF) media. 5. Glucose, glycol, glycer+100 ng/ml glial cell lines derived neurotrophic factor (GDNF) media and 6. Glucose, glycol and glycer+100 ng/ml tauroursodeoxycholic acid (TUDCA) media; after 7 days, the number of regenerating neurites was counted under a phase-contrast microscope. The explants were immunostained for NF-kB and SP1 transcription factors. Statistical analyses were performed by one-way ANOVA. Results: In retinas incubated with AGEs, the numbers of regenerating neuritis were fewer than in control. Neurotrophic factors increased the number of neurites but more significantly in the NT-4 group. The numbers of NF-kB and SP1 immunopositive cells were higher in retinas exposed to AGEs than in control. Neurotrophic factors decreased the number of NF-kB immunopositive cells but did not significantly affect SP-1 expression. NT-4 shows the best neuroprotective and regenerative effect. Conclusions: High dose AGEs impede neurite regeneration. The inhibition of regeneration is correlated with increased expression of NF-kB and SP1. NT-4 enhances neurite regeneration in AGEs exposed retinas more than other neurotrophic factors such as HGF, GDNF and TUDCA. The regenerative effect of NT-4 is correlated with NF-kB suppression.
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