Neuroscience letters · 2019
Carnosine decreases retinal ganglion cell death in a mouse model of optic nerve crushing.
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Kim Hwang Gyun, Heo Hwan, Sung Mi Sun, Park Sang Woo
Аннотация
PURPOSE: The objectives of this study were to investigate whether carnosine can increase retinal ganglion cell (RGC) survival in the mouse retina and to determine the possible association between nuclear factor-kappa B (NF-κB) mediated oxidative stress and neuroprotection of RGCs following optic nerve crushing (ONC).
METHODS: C57BL/6 J mice underwent ONC and were treated with carnosine (250 mg/kg) or saline intraperitoneally once daily until sacrifice. Peroxisome proliferator activated receptor (PPAR)-γ and glial fibrillary acidic protein (GFAP) expression were assessed at 1, 3, and 7 days after ONC. The effects of carnosine on the expression of PPAR-γ, GFAP, and NF-κB were assessed. To evaluate the effects of carnosine on mitochondrial biogenesis and function, we compared the expression of PPAR gamma coactivator-1α (PGC-1α) and mitochondrial transcription factor A (mtTFA) in retinas from mice that were treated with carnosine or saline at 3 days after ONC. RGC survival was assessed by labeling flat-mounted retinas with Brn3a at 2 weeks after ONC.
RESULTS: The expression levels of PPAR-γ and GFAP were upregulated in saline-treated retinas for 7 days after ONC, with maximal expression at 3 days, and carnosine treatment effectively attenuated this upregulation. In addition, upregulation of NF-κB, PGC-1α and mtTFA expression was also observed in saline-treated retinas after ONC, and this upregulation was blocked by carnosine treatment, resulting in a significant difference between carnosine-treated and saline-treated retinas after ONC. Immunohistochemical staining for Brn3a also showed that carnosine treatment protected against RGC loss after ONC.
CONCLUSIONS: Inhibition of NF-κB expression and oxidative stress by carnosine treatment plays a significant role in the prevention of RGC loss after ONC. The results also highlight the potential of carnosine as a neuroprotective agent against RGC loss in optic neuropathy.
METHODS: C57BL/6 J mice underwent ONC and were treated with carnosine (250 mg/kg) or saline intraperitoneally once daily until sacrifice. Peroxisome proliferator activated receptor (PPAR)-γ and glial fibrillary acidic protein (GFAP) expression were assessed at 1, 3, and 7 days after ONC. The effects of carnosine on the expression of PPAR-γ, GFAP, and NF-κB were assessed. To evaluate the effects of carnosine on mitochondrial biogenesis and function, we compared the expression of PPAR gamma coactivator-1α (PGC-1α) and mitochondrial transcription factor A (mtTFA) in retinas from mice that were treated with carnosine or saline at 3 days after ONC. RGC survival was assessed by labeling flat-mounted retinas with Brn3a at 2 weeks after ONC.
RESULTS: The expression levels of PPAR-γ and GFAP were upregulated in saline-treated retinas for 7 days after ONC, with maximal expression at 3 days, and carnosine treatment effectively attenuated this upregulation. In addition, upregulation of NF-κB, PGC-1α and mtTFA expression was also observed in saline-treated retinas after ONC, and this upregulation was blocked by carnosine treatment, resulting in a significant difference between carnosine-treated and saline-treated retinas after ONC. Immunohistochemical staining for Brn3a also showed that carnosine treatment protected against RGC loss after ONC.
CONCLUSIONS: Inhibition of NF-κB expression and oxidative stress by carnosine treatment plays a significant role in the prevention of RGC loss after ONC. The results also highlight the potential of carnosine as a neuroprotective agent against RGC loss in optic neuropathy.