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S. A. Hussong, R. J. Kapphahn, H. Roehrich, M. Maldonado, M. T. Pardue, D. A. Ferrington; Decreased Retinal Function in Immunoproteasome-Deficient Mice. Invest. Ophthalmol. Vis. Sci. 2010;51(13):5968.
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Immunoproteasome produces antigenic peptides for MHC class I presentation. In the immune-privileged retina, immunoproteasome is present in high concentrations under normal conditions and is upregulated with injury that does not involve inflammation (Ferrington et al., J Neurochem 2008). These data suggest immunoproteasome performs functions unrelated to its role in the immune system. To directly test this hypothesis, the current study examines retinal function and morphology in immunoproteasome-deficient mice.
Two strains of immunoproteasome-deficient mice lacking either one (lmp7-/- (L7)) or two (lmp7-/-mecl-1-/- (L7M1)) immunoproteasome subunits were compared with wild-type (WT) to investigate the potential function of immunoproteasome in the retina. Retinal function was assessed using electroretinography under dark-and light-adapted conditions. Relative abundance of photoreceptors was measured by slot-blot immunoassay for rhodopsin (rods) and opsin (cones). Rod and cone bipolar cell composition was determined by counting the cells stained with antibodies specific to bipolar cells (Chx10) and rod bipolar cells (PKCα).
Both strains of immunoproteasome-deficient mice exhibited significant alterations in ERG waveforms in response to light. Specific changes included: (1) ERG a-wave amplitudes were significantly lower in response to a high intensity flash (p<0.03), (2) ERG b-wave amplitudes were significantly decreased (p<0.001), (3) oscillatory potential implicit times in response to low intensity flashes were significantly delayed (p=0.004). These functional defects in immunoproteasome-deficient mice were not due to changes in retinal morphology. No difference in photoreceptor content or bipolar cell number for rods or cones was observed.
Immunoproteasome is essential for maintaining normal retinal function but does not affect overall retinal morphology. These results suggest immunoproteasome may be involved in transmission of the visual signal through the retina.
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