A novel role for the immunoproteasome in retinal function.
OBJECTIVE
The immunoproteasome is a proteasome subtype with a well-characterized role in the immune system. The presence of high immunoproteasome concentrations in the photoreceptors and synaptic regions of the immune-privileged retina implies a role in visual transmission. In this study, immunoproteasome knockout (KO) mice lacking either one (lmp7(-/-), L7) or two (lmp7(-/-)/mecl-1(-/-), L7M1) catalytic subunits of the immunoproteasome were used to test the hypothesis that it is essential for the maintenance of normal retinal function.


METHODS
Wild-type (WT) and immunoproteasome KO mice lacking either one (L7) or two (L7M1) catalytic subunits of the immunoproteasome were studied to determine the importance of the immunoproteasome in maintaining normal retinal function and morphology. Changes in retinal morphology were assessed in mice 2 to 24 months of age. Retinal function was measured with electroretinography (ERG), and relative content of select retinal proteins was assessed by immunoblot analysis.


RESULTS
Retinal morphometry showed no major abnormalities in age-matched WT or KO mice. No significant difference was observed in the levels of proteins involved in vision transmission. ERGs from KO mice exhibited an approximate 25% decrease in amplitude of the dark- and light-adapted b-waves and faster dark-adapted b-wave implicit times.


CONCLUSIONS
Immunoproteasome deficiency causes defects in bipolar cell response. These results support a previously unrecognized role for the immunoproteasome in vision transmission.
Hussong
Stacy A
SA
Department of Ophthalmology, University of Minnesota, Minneapolis, Minnesota, USA.
Roehrich
Heidi
H
Kapphahn
Rebecca J
RJ
Maldonado
Marcela
M
Pardue
Machelle T
MT
Ferrington
Deborah A
DA
D000375:Aging / Q000502:physiology; D000818:Animals; D017209:Apoptosis; D020134:Catalytic Domain; D003546:Cysteine Endopeptidases / Q000502:physiology*; D004596:Electroretinography; D019084:Fluorescent Antibody Technique, Indirect; D020868:Gene Silencing; D007107:Immune System / Q000502:physiology; D015151:Immunoblotting; D020287:In Situ Nick-End Labeling; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046988:Proteasome Endopeptidase Complex / Q000502:physiology*; D012160:Retina / Q000166:cytology / Q000502:physiology*; D051245:Retinal Bipolar Cells / Q000502:physiology; D014785:Vision, Ocular / Q000502:physiology
D003546:Cysteine Endopeptidases; C077436:LMP7 protein; D046988:Proteasome Endopeptidase Complex; C490920:Psmb10 protein, mouse