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Guzel Bikbova, Toshiyuki Oshitari, Shuichi Yamamoto; JNK and p38 expression involved in regenerative effect of different neurotrophic factors in rat retinas exposed to AGEs. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3627.
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© ARVO (1962-2015); The Authors (2016-present)
To determine the relationship between the expression of c-Jun N-terminal kinase (JNK) and p38 and the neuroprotective and regenerative effects of neurotrophic factors in rat retinas exposed to advanced glycation end-products (AGEs).
All of the procedures conformed to the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research. Retinal explants of 7 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 3) glucose +100 ng/ml neurotrophin 4 (NT-4) media; 4) glucose +100 ng/ml hepatocyte growth factor (HGF) media; 5) glucose +100 ng/ml glial cell line derived neurotrophic factor (GDNF) media; or 6) glucose +100 ng/ml tauroursodeoxycholic acid (TUDCA) media. The number of regenerating neurites was counted under a phase-contrast microscope after 7 days of culture. The explants were also immunostained for JNK and p38 after 24 hours and 7 days of culture. Statistical analyses were performed by one-way ANOVA.
In retinas incubated in media containing AGEs, the number of regenerating neuritis was fewer than in control media. The neurotrophic factors increased the number of neurites, and more significantly in the NT-4 media. The numbers of JNK and p38 immunopositive cells were higher in retinas exposed to AGEs than in control media after 24 hours of exposure. However after 7 days, only the number of JNK immunopositive cells was increased. Neurotrophic factors decreased the number of JNK and p38 immunopositive cells. NT-4 had the best neuroprotective and regenerative effects.
Increases in the JNK and p38 expression are associated with neuronal cell death and regeneration in AGEs-exposed rat retinas.
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