LIGHT-INDUCED RETINAL DEGENERATION SUPPRESSES DEVELOPMENTAL PROGRESSION OF FLIP-TO-FLOP ALTERNATIVE SPLICING IN GLUR1

Citation
T. Harada et al., LIGHT-INDUCED RETINAL DEGENERATION SUPPRESSES DEVELOPMENTAL PROGRESSION OF FLIP-TO-FLOP ALTERNATIVE SPLICING IN GLUR1, The Journal of neuroscience, 18(9), 1998, pp. 3336-3343
Citations number
41
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences
Journal title
ISSN journal
0270-6474
Volume
18
Issue
9
Year of publication
1998
Pages
3336 - 3343
Database
ISI
SICI code
0270-6474(1998)18:9<3336:LRDSDP>2.0.ZU;2-Y
Abstract
AMPA receptors are hetero-oligomers composed of subsets of four distin ct subunits, termed GluR1, GluR2, GluR3, and GluR4. Using quantitative reverse transcription-PCR analysis, we have found that light-induced degeneration of rat retina dramatically suppresses developmental progr ession of the flip-to-flop alternative splicing switch of retinal GluR 1 mRNA. When animals were raised under standard conditions of a 12 hr light/dark cycle (LD 12:12), the flop-to-flip ratio in GluR1 and GluR2 dramatically increased between postnatal day 10 (P10) and P28, and th e ratios continued to increase gradually up to P84. When animals were raised in complete darkness, this increase was delayed in GluR1 betwee n P21 and P42. In addition, the increase of the flop-to-flip ratio in GluR1 was strongly suppressed after P21 under conditions of continuous illumination from P2. This is significant because P21 is just after t he eye opening and is the timing of the onset of light-induced retinal degeneration. This suppression of the increase of the flop-to-flip ra tio was specific to GluR1 and was not observed in GluR2-4. Immunocytoc hemistry and immunoblot analysis suggested no changes in either the di stribution or expression of GluR1 protein in the light-damaged retina measured at P84. When rats were raised under continuous illumination f rom P2 to P21 followed by LD 12:12 from P22 to P84, retinal degenerati on did not progress after P22. In such animals the flop-to-flip ratio, once decreased to similar to 50% of the control (LD 12:12) at P21, wa s restored to the control level at P84. These findings demonstrate tha t developmental progression of the flip-to-flop exon switch in retinal GluR1 is affected by lighting conditions, and that light-induced reti nal degeneration contributes to the mechanism of suppression of this s plicing switch.