Branched-Chain Amino Acids Enhance Retinal Ganglion Cell Survival and Axon Regeneration after Optic Nerve Transection in Rats

ABSTRACT

Purpose

This study’s aim was to investigate the beneficial effects of branched-chain amino acids (BCAAs) on the neuronal survival and axon regeneration of retinal ganglion cells (RGCs) after optic nerve (ON) transection.

Method

The experimental rats received daily BCAA injections through the caudal vein after left intra-orbital ON transection. Neuroprotection was evaluated by counting Fluorogold-labeled RGCs. The role of mammalian target of rapamycin (mTOR) pathway activation in promoting RGC survival was studied after rapamycin administration. Moreover, a peripheral nerve (PN) graft was transplanted onto the transected ON to study the effects of BCAAs on axon regeneration of injured RGCs.

Results

Our results showed that BCAAs alleviated the death of RGCs 7 and 14 days after ON transection, accompanied by an activation of mTOR pathway in RGCs. Blocking mTOR pathway with rapamycin eliminated such neuroprotective effects of BCAAs. Moreover, BCAAs also promoted axon regeneration of injured RGCs into a PN graft.

Conclusion

Our results suggest a neuroprotection of BCAAs through the activation of mTOR pathway. BCAAs also have a beneficial effect on axon regeneration of injured RGCs. Therefore, BCAAs could be considered for the clinical treatment of ON injury.

KEYWORDS:

• Branched-chain amino acids
• retinal ganglion cell
• neuroprotection
• axon regeneration
• mTOR

Conflicts of interest

This study has no conflict of interest.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China [No. 81670846, 81302451, and 81470631]; Natural Science Foundation of Shaanxi Province of China [No. 2018JM7036 and 2016SF-171]; and the National Basic Research Program of China [No. 2014CB542202].