Involvement of endoplasmic reticulum stress in optic nerve degeneration after chronic high intraocular pressure in DBA/2J mice

DBA/2J mice are one of several animal strains used for experimental models of both intraocular hypertension and glaucoma. This study investigates the relationship between endoplasmic reticulum (ER) stress and optic nerve degeneration in DBA/2J mice. Intraocular pressure (IOP) was measured in DBA/2J mice between the ages of 6 and 15 months. Optic nerve damage was assessed at 15 months of age. The nerve was immunostained with antibodies to either neurofilament heavy chain (NFH) or phosphorylated NFH (pNFH), and optic nerve damage was assessed by performing NFH- and pNFH-positive axon counts. Expression levels of the ER stress proteins 78-kDa glucose-regulated protein, also known as binding immunoglobulin protein, and C/EBP homologous protein were assayed with Western blotting. We also investigated ER stress localization in the optic nerve by double immunostaining with antibodies to ionized calcium-binding adaptor molecule 1, myelin basic protein, and glial fibrillary acidic protein (GFAP). In DBA/2J mice, IOP began to rise at 8 months of age, and retinal degeneration was detected at 15 months of age. DBA/2J mice had fewer axons than controls at 15 months of age. ER stress-related protein levels were higher in the optic nerves of DBA/2J mice and were colocalized with GFAP-positive astrocytes. Our findings suggest that ER stress plays a role in optic nerve degeneration during chronic ocular hypertension. Furthermore, ER stress may be related in some way to astrocyte activation. (C) 2015 Wiley Periodicals, Inc.