The Role of Telomere Maintenance in Adult Mammalian Acute Central Nervous System Injury and Retinal Ganglion Cell Apoptosis

Telomeres are DNA-protein complexes that cap eukaryotic chromosome ends. They have dynamic secondary structures that interact with networks of telomere-associated proteins, protecting genomic integrity and maintaining proliferative success of cells. When telomeres are destabilized, chromosome ends are misrecognized as DNA double-stranded breaks eliciting DNA damage responses that lead to cellular apoptosis. There is sparse evidence that telomere destabilization plays a role in the pathology of central nervous system (CNS) insults. This study examines this possibility during the acute injury-induced degeneration and apoptosis of retinal ganglion cells (RGCs). By administering or knocking-down key telomere-associated proteins, this work demonstrates that TERT expression promotes RGC survival while Telomerase activity has no role, that TCAB1, TRF1, Ku70, and EST1A play important roles in RGC survival while TRF2 and DNA PKcs do not, and that, overall, telomere maintenance cannot be eliminated as a contributing factor in RGC degeneration and apoptosis within the acutely injured CNS.M.Sc