| Authors |
Berkowitz BA, Gorgis J, Patel A, Baameur F, Gurevich VV, Craft CM, Kefalov VJ,
Roberts R
|
| Submitted By |
Bruce Berkowitz on 11/3/2014 |
| Status |
Published |
| Journal |
FASEB journal : official publication of the Federation of American Societies for Experimental Biology |
| Year |
2014 |
| Date Published |
10/28/2014 |
| Volume : Pages |
29 : 554 - 564 |
| PubMed Reference |
|
| Abstract |
Rod tetrameric arrestin 1 (tet-ARR1), stored in the outer nuclear layer/inner
segments in the dark, modulates photoreceptor synaptic activity; light exposure
stimulates a reduction via translocation to the outer segments for terminating
G-protein coupled phototransduction signaling. Here, we test the hypothesis that
intraretinal spin-lattice relaxation rate in the rotating frame (1/T1?), an
endogenous MRI contrast mechanism, has high potential for evaluating rod
tet-ARR1 and its reduction via translocation. Dark- and light-exposed mice (null
for the ARR1 gene, overexpressing ARR1, diabetic, or wild type with or without
treatment with Mn(2+), a calcium channel probe) were studied using 1/T1? MRI.
Immunohistochemistry and single-cell recordings of the retinas were also
performed. In wild-type mice with or without treatment with Mn(2+), 1/T1? of
avascular outer retina (64% to 72% depth) was significantly (P < 0.05) greater
in the dark than in the light; a significant (P < 0.05) but opposite pattern was
noted in the inner retina (<50% depth). Light-evoked outer retina ?1/T1? was
absent in ARR1-null mice and supernormal in overexpressing mice. In diabetic
mice, the outer retinal ?1/T1? pattern suggested normal dark-to-light tet-ARR1
translocation and chromophore content, conclusions confirmed ex vivo.
Light-stimulated ?1/T1? in inner retina was linked to changes in blood volume.
Our data support 1/T1? MRI for noninvasively assessing rod tet-ARR1 and its
reduction via protein translocation, which can be combined with other metrics of
retinal function in vivo.-Berkowitz, B. A., Gorgis, J., Patel, A., Baameur, F.,
Gurevich, V. V., Craft, C. M., Kefalov, V. J., Roberts, R. Development of an MRI
biomarker sensitive to tetrameric visual arrestin 1 and its reduction via
light-evoked translocation in vivo.
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