title: Neurite regeneration in adult rat retinas exposed to advanced glycation end-products and regenerative effects of neurotrophin-4.
abstract: The purpose of this study was to determine the effect of low concentrations of advanced glycation end-products on neurite regeneration in isolated rat retinas, and to determine the effects of neurotrophin-4 on regeneration in advanced glycation end-products exposed retinas. Retinal explants of 4 adult Sprague-Dawley rats were cultured on collagen gel and were incubated in; (1) serum-free control culture media, (2) glucose-advanced glycation end-products-bovine serum albumin media, (3) glycolaldehyde-advanced glycation end-products-bovine serum albumin media, (4) glyceraldehyde-advanced glycation end-products-bovine serum albumin media, (5) glucose-advanced glycation end-products+neurotrophin-4 media, (6) glycolaldehyde-advanced glycation end-products+neurotrophin-4 media, or (7) glyceraldehyde-advanced glycation end-products+neurotrophin-4 supplemented culture media. After 7 days, the number of regenerating neurites from the explants was counted. Then, explants were fixed, cryosectioned, and stained for TUNEL. The ratio of TUNEL-positive cells to all cells in the ganglion cell layer was determined. Immunohistochemical examinations for the active-form of caspase-9 and apoptosis-inducing factor were performed. In retinas incubated with advanced glycation end-products containing media, the number of regenerating neurites were fewer than in retinas without advanced glycation end-products, and the number of TUNEL-positive cells and caspase-9- and apoptosis-inducing factor-immunopositive cells was significantly higher than in control media. Neurotrophin-4 supplementation increased the numbers of regenerating neuritis, and the number of TUNEL-positives, caspase-9-, and apoptosis-inducing factor-immunopositive cells were significantly fewer than that in advanced glycation end-products without neurotrophin-4 media. Low doses of advanced glycation end-products impede neurite regeneration in the rat retinas. Neurotrophin-4 significantly enhances neurite regeneration in retinas exposed to advanced glycation end-products.
authors: Department of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine, Inohana 1-8-1, Chuo-ku, Chiba 260-8670, Chiba, Japan.
authors: Guzel
authors: G
authors: Bikbova
authors: Toshiyuki
authors: T
authors: Oshitari
authors: Shuichi
authors: S
authors: Yamamoto
mesh_terms: D000818:Animals; D017209:Apoptosis; D017127:Glycation End Products, Advanced / Q000494:pharmacology*; D008297:Male; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009416:Nerve Regeneration / Q000187:drug effects; D016501:Neurites / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012165:Retinal Ganglion Cells / Q000502:physiology* / Q000648:ultrastructure
chemical_list: D017127:Glycation End Products, Advanced; D009414:Nerve Growth Factors; C073922:neurotrophin 4
keywords: 4,6-diamidino-2-phenyl indole; AGE; AGEs; AIF; ANOVA; Apoptosis; BSA; Caspase-9; DAPI; GCL; INL; NT-4; ONL; RAGE; RGCs; Regeneration; SD; Sprague-Dawley; TUNEL; TdT-dUTP terminal nick-end labeling; VEGF; advanced glycation end-products; analysis of variance; apoptosis-inducing factor; bovine serum albumin; ganglion cell layer; inner nuclear layer; neurotrophin-4; outer nuclear layer; receptor for AGE; retinal ganglion cells; vascular endothelial neurotrophic factor