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T. Oshitari, N. Yoshida-Hata, S. Yamamoto; Enhancement of Neurite Regeneration in Isolated Adult Rat Diabetic Retinas by Neurotrophic Factors and Citicoline. Invest. Ophthalmol. Vis. Sci. 2009;50(13):107.
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To determine whether brain-derived neurotrophic factor (BDNF), neurotrophin-4 (NT-4), vascular endothelial growth factor (VEGF)120, VEGF164, and citicoline enhance the regeneration of neurites in isolated retinas exposed to high glucose in the medium.
Six adult SD rats were studied. After killing rats, the retinas were isolated, and retinal explants were embedded in a collagen gel and cultured in serum-free medium. One group of explants was cultured in normal glucose medium and another group in high glucose medium. In addition, BDNF, NT-4, VEGF120, VEGF164, or citicoline were added to each type of media. After seven days in culture, the number of neurites was counted in the explants cultured in the two types of media containing the neurotrophic factors or citicoline under a phase contrast microscope. Statistical analysis was performed with the Mann Whitney U test.
The number of regenerating neurites in the retinas cultured in the high glucose medium was significantly fewer than those cultured in the normal glucose medium (77.7±13.3/mm2 versus 37.8±7.0/mm2; P <0.01). The number of regenerating neurites was significantly increased in retinas incubated with NT-4 and BDNF in normal glucose medium over the number in retinas incubated in normal glucose without NT-4 and BDNF (191.4±45.4/mm2 versus 77.7±13.3/mm2; P <0.01, 212.4±52.0/mm2 versus 77.7±13.3/mm2; P <0.01, respectively). The numbers of regenerating neurites were significantly higher in retinas incubated with NT-4, BDNF, or citicoline in high glucose media than in high glucose media without NT-4, BDNF, or citicoline (187.5±50.5/mm2 versus 37.8±7.0/mm2; P <0.01, 119.4±31.1/mm2 versus 37.8±7.0/mm2; P <0.01, 63.9±14.1/mm2 versus 37.8±7.0/mm2; P <0.01, respectively). VEGF120 and VEGF164 did not affect the number of regenerating neurites in both normal and high glucose media (77.4±23.5/mm2 versus 77.7±13.3/mm2, 61.8±13.1/mm2 versus 77.7±13.3/mm2, 47.2±17.7/mm2 versus 37.8±7.0/mm2, 55.6±20.0/mm2 versus 37.8±7.0/mm2, respectively).
Incubating retinas in high glucose medium reduces the number of regenerating neurites in isolated adult rat retinas. BDNF, NT-4, and citicoline enhance the regeneration of neurites in the retinas incubated in high glucose medium. VEGF120 and VEGF164 do not affect neurite regeneration in adult rat retinas incubated in high glucose medium.
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