Abstract
Purpose: :
To investigate the involvement of endoplasmic reticulum (ER) stress in retinal ganglion cell (RGC) death using an axotomized rat model.
Methods: :
We transected the optic nerve 2 mm posterior to the globe in Sprague-Dawley rats; retinal tissue was then collected at 1, 3, 5, 7, and 14 days. The levels of ER stress proteins (BiP, phosphorylated PERK [p-PERK], phosphorylated eukaryotic initiation factor 2 (p-eIF2α) and C/EBP-homologous protein [CHOP]) were evaluation in both western blot analysis and immunohistochemical staining.
Results: :
The levels of ER stress proteins (BiP, p-PERK, p-eIF2α and CHOP), increased throughout the observation period. Immunohistochemistry revealed p-PERK expression in the ganglion cell layer (GCL), inner plexiform layer (IPL), and inner nuclear layer (INL), whereas CHOP was expressed primarily in the GCL. In rat retina, the co-expression of p-PERK and CHOP was observed in RGCs. The up-regulation of these proteins coincided with or preceded RGC apoptosis, as indicated by TUNEL staining.
Conclusions: :
These results suggest that ER stress plays a role in RGC death after axotomy. Thus, ER stress modulators may be candidate therapeutic agents against RGC death in conditions such as glaucoma.