Purchase this article with an account.
D. S. Gregerson, H. Roehrich, S. Hussong, D. A. Ferrington; Alternative Roles for Immunoproteasome - Repairing and Protecting From Retinal Damage. Invest. Ophthalmol. Vis. Sci. 2007;48(13):2944.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Immunoproteasome is well-known for its essential role in generating peptides for MHC Class I occupancy, providing opportunity for CD8 T cell recognition of potential antigens. Expression of the proteasome subunits that define the immunoproteasome as distinct from constitutive proteasome is upregulated by pro-inflammatory cytokines including IFN-gamma and TNF-alpha. Recently, evidence of immunoproteasome has been found in some injured and regenerating tissues, including muscle. Since the retina is continually challenged by its environment, we examined the retina for expression of subunits associated with immunoproteasome under normal and injured conditions.
Tissues, including retina and brain, were analyzed for expression of subunits specific for the immunoproteasome including LMP2 and LMP7, and subunits specific for constitutive proteasome, including beta1 and beta5. Immunohistochemistry and western blotting were used to detect and quantitate their expression. Distinct mechanisms of injury were provided by cytotoxic T cell (CTL) attack on glia and neurons, or by non-inflammatory damage (optic nerve crush).
Normal, uninjured retina expresses substantial levels of subunits specifically associated with immunoproteasome in glia, neurons, RPE, and bone marrow-derived cells. Retinal injury further promoted immunoproteasome subunit expression. Expression in retina was concentrated in RIS, OPL, and IPL, and it's distribution was affected by injury. Conversely, immunoproteasome was not detected in normal brain parenchyma. Only bone marrow-derived cells in the meninges of normal brain expressed immunoproteasome. Following inflammation induced by CTL attack, cells in parenchymal lesions in the brain upregulated immunoproteasome, which then decreased as the lesions resolved.
Immunoproteasome was readily detected in normal retina, but not brain. Expression in both tissues was upregulated by injury. It is proposed that the normal, day-to-day existence and function of the retina is itself sufficiently challenging as to require on-going expression of immunoproteasome to maintain homeostasis of the tissue.
This PDF is available to Subscribers Only