Abstract
Purpose: :
One of the established roles for the immunoproteasome is the generation of antigenic peptides. However, its substantial expression in the immune-privileged retina implies other non-immune functions are possible. This study investigates how the immunoproteasome responds to retinal damage generated by optic nerve crush.
Methods: :
Optic nerve crush (ONC) was performed on one eye of each mouse. Both crushed and uncrushed eyes were subsequently harvested 1, 2, 11, 24 and 36 days later. Retinal homogenates were analyzed for glial fibrillary acidic protein (GFAP), a measure of retinal stress, and immunoproteasome subunits by Western immunoblotting. In addition, ganglion cell apoptosis and number were determined at 7, 14 and 21 days post-ONC from retinal sections stained with TUNEL and DAPI.
Results: :
ONC induced significant ganglion cell damage as determined by increased levels of GFAP and increased number of TUNEL positive cells in the ganglion cell layer (GCL). In addition, a time-dependent decrease in the number of GCL nuclei was observed. These indicators of retinal cell damage were observed only in the crushed eye and correlated with a significant upregulation in immunoproteasome.
Conclusions: :
The immunoproteasome is present in normal (control) retina and is significantly upregulated in response to ONC injury. The increase in immunoproteasome correlated with both increased retinal GFAP and increased TUNEL positive cells of the GCL. These results suggest a non-immune role for the immunoproteasome in responding to retinal stress.
Keywords: stress response • proteolysis • retina