 |
||||
|
||||
|
||||
|
||||
Previous Article | Next Article
The Journal of Neuroscience, May 1, 1998, 18(9):3336-3343
Light-Induced Retinal Degeneration Suppresses Developmental Progression of Flip-to-Flop Alternative Splicing in GluR1
Takayuki Harada1, 2, Chikako Harada1, 2, Masayuki Sekiguchi1, and Keiji Wada1 1 Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo 187-8502, Japan, and 2 Department of Ophthalmology, Hokkaido University School of Medicine, Kita-ku, Sapporo 060-8638, Japan
AMPA receptors are hetero-oligomers composed of subsets of four distinct 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 progression of the flip-to-flop alternative splicing switch of retinal GluR1 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 the ratios continued to increase gradually up to P84. When animals were raised in complete darkness, this increase was delayed in GluR1 between 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 the eye opening and is the timing of the onset of light-induced retinal degeneration. This suppression of the increase of the flop-to-flip ratio was specific to GluR1 and was not observed in GluR2-4. Immunocytochemistry and immunoblot analysis suggested no changes in either the distribution or expression of GluR1 protein in the light-damaged retina measured at P84. When rats were raised under continuous illumination from P2 to P21 followed by LD 12:12 from P22 to P84, retinal degeneration did not progress after P22. In such animals the flop-to-flip ratio, once decreased to ~50% of the control (LD 12:12) at P21, was restored to the control level at P84. These findings demonstrate that developmental progression of the flip-to-flop exon switch in retinal GluR1 is affected by lighting conditions, and that light-induced retinal degeneration contributes to the mechanism of suppression of this splicing switch.
Key words: flip and flop; AMPA; retina; quantitative reverse transcription-PCR; light/dark condition; retinal degeneration
Copyright © 1998 Society for Neuroscience 0270-6474/98/1893336-08$05.00/0
This article has been cited by other articles:
C. Harada, T. Harada, H.-M. A. Quah, K. Namekata, K. Yoshida, S. Ohno, K. Tanaka, and L. F. Parada
Role of Neurotrophin-4/5 in Neural Cell Death during Retinal Development and Ischemic Retinal Injury In Vivo
Invest. Ophthalmol. Vis. Sci., February 1, 2005; 46(2): 669 - 673.
[Abstract] [Full Text] [PDF]
T. Harada, C. Harada, S. Kohsaka, E. Wada, K. Yoshida, S. Ohno, H. Mamada, K. Tanaka, L. F. Parada, and K. Wada
Microglia-Muller Glia Cell Interactions Control Neurotrophic Factor Production during Light-Induced Retinal Degeneration
J. Neurosci., November 1, 2002; 22(21): 9228 - 9236.
[Abstract] [Full Text] [PDF]
T. Harada, C. Harada, Y. Mitamura, C. Akazawa, K. Ohtsuka, S. Ohno, S. Takeuchi, and K. Wada
Neurotrophic Factor Receptors in Epiretinal Membranes After Human Diabetic Retinopathy
Diabetes Care, June 1, 2002; 25(6): 1060 - 1065.
[Abstract] [Full Text] [PDF]
R. C. Carpenter, L. Miao, Y. Miyagi, E. Bengten, J. H. Zhang, and J. P. Muizelaar
Altered Expression of P2 Receptor mRNAs in the Basilar Artery in a Rat Double Hemorrhage Model Editorial Comment
Stroke, February 1, 2001; 32(2): 516 - 522.
[Abstract] [Full Text] [PDF]
|
|
|
|
 |
|