Carnosine decreases retinal ganglion cell death in a mouse model of optic nerve crushing

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).

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.

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.

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.