Telomerase expression and activity promote retinal ganglion cell survival after optic nerve injury

Abstract

Telomerase is a reverse transcriptase and includes two essential components: catalytic subunit TERT and RNA template TERC. It can protect chromosome ends during cell division. Recent studies demonstrated that telomerase can promote neuronal survival and has been implicated in repairing damaged nervous system. Retinal ganglion cells (RGCs) die by apoptosis after optic nerve (ON) injury in rodents, whereas no RGC death is observed in Cyprinidae (goldfish and zebrafish) after ON axotomy. A possible explanation for the difference in the vulnerability of RGCs to axotomy-induced cell death is the intrinsic capacity of the mammalian and fish RGCs to respond to injury. In our study, we found that telomerase activity, TERT mRNA and protein expression levels were increased significantly in zebrafish retina after ON crush when compared to those in the rat retina. This result indicated the difference of telomerase activity and TERT expression after ON injury might be one of the reasons accounted for the different survival abilities between mammalian and lower vertebrate RGCs. Brain-derived neurotrophic factor (BDNF) are known to enhance rat RGCs survival after axotomy. And BDNF can also increase telomerase activity and TERT expression level to exert neuroprotective effect in vitro. We have been examining whether the survival-promoting function of BDNF is mediated by telomerase after ON axotomy in rat. We found that after intravitreal injection of BDNF in ON-crushed rats, there were significant increases of telomerase activity, TERT mRNA and protein expression levels in the retina. While at the same time, we observed an increase in the phosphorylation of Erk1/2 and Akt and a decrease in Bax expression and activated caspase-3. Erk and Akt inhibitors abolished the effects of BDNF to increase TERT expression and promote RGC survival. These results suggested that BDNF increases TERT expression via the Erk1/2 and Akt signal pathways and TERT may play a role in mediating the protective effect of BDNF on rat RGC survival after ON injury.